What this page is for Tau Protein Corruption Aphanizomenon flos-aquae (AFA) Colostrinin (Cognisure) Sleep apnea NSAIDs Nicotine Saffron Leukine Actos Parkinson's Disease Licorice Root Extract Shutting Down Metformin Epothilone D 5-lipoxygenase Cat's Claw Lutein HSB-13 Lysine Herpes Simplex Virus PSD (post-synaptic density) Rosemary Exercise Bryostatin Transcranial magnetic stimulation (TMS) Genetics Liver

Anatabine Brain Inflammation Oligomers Zileuton PBT2 Prazosin REM Sleep Time C-reactive protein (CRP) NMS (Neuroleptic Malignant Syndrome) Haldol Memantine Ferulic Acid Diabetes and Dementia Bexarotene Trehalose

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Acetylation May Contribute to Dementia and Alzheimer's Disease; May Lead to New Treatments
ScienceDaily (Sep. 22, 2010)
A new study uncovers a protein modification that may contribute to the formation of neuron-damaging neurofibrillary tangles in the human brain. The research, published by Cell Press in the Sept. 23 issue of the journal Neuron, may lead to new strategies for treatment of neurodegenerative diseases that result from pathological aggregation of tau protein... While the link between tau acetylation and tau phosphorylation is not known, the results provide new insight into tau-mediated neuropathology. "Our findings support the model that the abnormally elevated acetylation at an early stage of the disease could block clearance of p-tau from neurons, leading to its accumulation. Our observation that p300 diminished tau acetylation and effectively eliminated p-tau supports the idea that interfering with tau acetylation may be a new approach for reducing tau-related pathology."
http://www.sciencedaily.com/releases/2010/09/100922121939.htm

Breakthrough Untangles One Key to Alzheimer’s Disease
By Rachael Rettner, MyHealth
NewsDaily Staff Writer
Sep 22, 2010 | 12:01 PM ET |

Scientists may have found a new way to reduce levels of a toxic protein that accumulates in the brains of Alzheimer's patients. The approach may one day lead to new therapies for the condition.

In patients with certain neurodegenerative diseases, including Alzheimer's, a protein called tau forms stringy blobs known as "tangles" inside brain cells. These tangles, along with brain plaques, are thought to contribute to the development of the disease.

Normally, tau proteins help maintain the cell's structure. But in Alzheimer's patients, they've become toxic because they've undergone a certain kind of chemical change, called phosphorylation. Brain cells should recognize that these changed tau proteins are damaged, and should destroy them. But this destruction doesn't happen, and scientists have not understood why.

Li Gan, a researcher at the Gladstone Institute of Neurological Disease in San Francisco, and her colleagues wondered whether these damaged tau proteins might be modified in some other way that prevents the cells from demolishing them.

They discovered a second chemical change that the toxic tau proteins have undergone, called acetylation, which makes them destruction-proof. In both mice with Alzheimer's and humans with Alzheimer's, levels of this destruction-proof tau protein were elevated at early and middle stages of the disease — before the tangles appeared.

And when they blocked the second change, levels of the damaging proteins in the cells were greatly diminished.

"We can actually make the cell more efficient," in getting rid of the damaged tau proteins, Gan told MyHealthNewsDaily.

The molecule the researchers used to block the second change might one day serve as a new class of anti-Alzheimer's disease drugs, Dr. Lennart Mucke, GIND director, said in a statement.

The researchers said the second change might work by preventing the toxic tau protein from being "tagged" for demolition by the cell.

The study will be published tomorrow (Sept. 23) in the journal Neuron.
http://myhealthnewsdaily.com/alzheimers-disease-tangles-tau-protein-100922-0418/

D-Ribosylated Tau forms globular aggregates with high cytotoxicity.
Chen L, Wei Y, Wang X, He R.
State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, 100101 Beijing, China.
Cell Mol Life Sci. 2009 Aug;66(15):2559-71. Epub 2009 Jun 11.

Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer's disease has been widely studied, little attention has been paid to the role of D-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of D-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that D-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that D-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity.
PMID: 19517062
http://www.ncbi.nlm.nih.gov/pubmed/19517062?ordinalpos=1&itool=PPMCLayout.PPMCAppController.PPMCArticlePage.PPMCPubmedRA&linkpos=1

Dynamics of Chaperone Protein Critical in Rescuing Brains of Alzheimer's Mice from Neuron Damage

ScienceDaily (Dec. 3, 2010) — Dynamic regulation of the chaperone protein Hsp27 was required to get rid of abnormally accumulating tau in the brains of mice genetically modified to develop the memory-choking tau tangles associated with Alzheimer's disease, a University of South Florida-led study found...
http://www.sciencedaily.com/releases/2010/12/101203091449.htm


Alzheimer's: Tau Disrupts Neural Communication Prior to Neurodegeneration

ScienceDaily (Dec. 24, 2010) — A new study is unraveling the earliest events associated with neurodegenerative diseases characterized by abnormal accumulation of tau protein. The research, published in the December 22 issue of the journal Neuron, reveals how tau disrupts neuronal communication at synapses and may help to guide development of therapeutic strategies that precede irreversible neuronal degeneration...
http://www.sciencedaily.com/releases/2010/12/101222121500.htm

Tau-Induced Memory Loss in Alzheimer’s Mice Is Reversible; Study Raises Hopes for the Development of Effective Therapies

ScienceDaily (Feb. 17, 2011) —  ...However, it appears that the toxic effect of tau protein is largely eliminated when the corresponding tau gene is switched off. Researchers from the Max Planck Research Unit for Structural Molecular Biology at DESY in Hamburg have succeeded in demonstrating that once the gene is deactivated, mice with a human tau gene, which previously presented symptoms of dementia, regain their ability to learn and remember, and that the synapses of the mice also reappear in part... Whereas aggregated amyloid-beta protein forms insoluble clumps between the neurons, the tau protein accumulates inside them. Tau protein stabilises the tube-shaped fibers of the cytoskeleton, known as microtubules, which provide the "rails" for cellular transport. In Alzheimer disease, excess phosphate groups cause the tau protein to malfunction and form clumps (the 'neurofibrillary tangles'). As a result, nutrient transport breaks down and the neurons and their synapses die off. This process is accompanied by the initial stage of memory loss... The scientists concluded from this that mutated or pathological tau can alter healthy tau...
http://www.sciencedaily.com/releases/2011/02/110216083119.htm

Increasing Brain Enzyme May Slow Alzheimer's Disease Progression; Study Finds Damaging Accumulation of Tau Proteins Removed

ScienceDaily (Feb. 16, 2011) — ..."Our research demonstrated that increasing the brain enzyme known as PSA/NPEPPS can effectively block the accumulation of tau protein that is toxic to nerve cells and slow down the progression of neural degeneration without unwanted side effects," said Stanislav L. Karsten, PhD, the corresponding author for the study and a principal investigator at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed). "These findings suggest that increasing this naturally occurring brain peptidase, PSA/NPEPPS, may be a feasible therapeutic approach to eliminate the accumulation of unwanted toxic proteins, such as tau, that cause the neural degeneration associated with the devastating effects of Alzheimer's disease and other forms of dementia."...
http://www.sciencedaily.com/releases/2011/02/110216110538.htm

Blue Green Algae health benefit
Blue green algae are not really algae, but they actually are more closely related to bacteria. Because they are photosynthetic and aquatic, cyanobacteria are often called "blue-green algae". This name is convenient for talking about organisms in the water that make their own food, but does not reflect any relationship between the cyanobacteria and other organisms called algae. Cyanobacteria are relatives of the bacteria, not eukaryotes. Cyanobacteria are aquatic and photosynthetic, that is, they live in the water, and can manufacture their own food. Because they are bacteria, they are quite small and usually unicellular, though they often grow in colonies large enough to see. They have the distinction of being the oldest known fossils, more than 3.5 billion years old. Cyanobacteria are still around; they are one of the largest and most important groups of bacteria on earth.

The two types of Blue-Green Algae

Blue green algae are an important part of the food chain in lakes and ponds worldwide. The two main blue-green types are Spirulina and Aphanizomenon flos-aquae (AFA). AFA is harvested from Upper Klamath Lake in Oregon and then freeze-dried and sold in capsules and other forms...
http://www.raysahelian.com/bluegreenalgae.html

(WO/2008/000430) ALPHANIZOMENON [sic] FLOS AQUAE PREPARATION, EXTRACTS AND PURIFIED COMPONENTS THEREOF FOR THE TREATMENT OF NEUROLOGICAL, NEURODEGENERATIVE AND MOOD DISORDERS

Inventors:  SCOGLIO, Stefano; (IT).
            CANESTRARI, Franco; (IT).
            BENEDETTI, Serena; (IT).
            BENEDETTI, Yanina; (IT).
            DELGADO-ESTEBAN, Maria; (ES).

WO 2008000430 20080103

APHANIZOMENON FLOS AQUAE PREPARATION, EXTRACTS AND PURIFIED COMPONENTS THEREOF FOR THE TREATMENT OF NEUROLOGICAL, NEURODEGENERATIVE AND MOOD DISORDERS

The present invention relates to the microalga Aphanizomenon Flos Aquae Aquae Ralfs ex Born. & Flah. Var. flos aquae (AFA Klamath). More precisely, the invention provides extracts of AFA Klamath and purified components thereof useful for the prevention or treatment of neurological, neurodegenerative and mood conditions or diseases... Phenylethylamine (PEA) is an endogenous amine synthesized by decarboxylation of phenylalanine in dopaminergic neurons of the nigrostriatal system, and may act as a neuromodulator of catecholamine neurotransmission in the brain... Moreover, once ingested PEA can easily pass through the blood-brain barrier and stimulate the release of dopamine from the nigrostriatal tissue even at low dosages...

Description of the invention

The invention is based on the identification, in the microalga Aphanizomenon Flos Aquae Aquae Ralfs ex Born. & Flah. Var. flos aquae (AFA Klamath), of substances that, alone or in combination, exert beneficial effects on various neurological diseases, conditions, dysfunctions or disorders, including neurodegenerative diseases such as Alzheimer's and Parkinson's, multiple sclerosis, hyperactivity and attention deficit disorders (ADHD), autism, depression, memory deficit and mood disturbances. In particular, it has been found that AFA Klamath microalga contains, besides phenylethylamine, which is a neuromodulator characterized by dopaminergic and noradrenergic activity, specific molecules which quite surprisingly proved to be very effective inhibitors of the enzyme monoaminoxidase B (MAO-B), namely: a) the specific AFA-phytochrome; b) the AFA-phycobiliprotein complex containing a phycobilisome formed by C-phycocyanin (C-PC) and phycoerythrocyanin (PEC, including its chromophore phycoviolobilin or PVB) ("AFA-phycocyanins"); c) mycosporine-like amino acids or MAAs. This finding is very important since the PEA contained in the algae, unless protected by MAO-B inhibitors, would be rapidly destroyed upon ingestion by the MAO-B enzyme...

...the AFA Klamath extract... is prepared by [either]: a) freezing the freshly harvested AFA alga and thawing it, or, if... dried AFA powder, sonicating the water-diluted AFA powder to disrupt the cells; b) centrifuging the product of step a) to separate the supernatant... from the precipitate...; c) collecting the supernatant containing the water-soluble components.

The resulting product is an extract (indicated as "Basic Extract") which concentrates PEA as well as other synergic molecules such as the AFA phytochrome, the AFA-phycocyanins, and the MAAs. For example, whereas Klamath microalga has a natural content of PEA ranging from 2 to 4 mg/gr, the Basic Extract increases this concentration to a level ranging from 9 to 11 mg/gr (HPLC analysis).

It is possible to further purify the extract by passing it through an ultra- filtration system...

The Basic Extract obtained by steps a) to c), i.e. without ultra-filtration, is generally preferred as it contains the most appropriate amounts of PEA, AFA-phytochrome, AFA-PC and MAAs. Moreover, this Basic Extract also includes substances such as chlorophyll and carotenes, even though in a reduced proportion, contributing to its antioxidant and anti-inflammatory properties...
http://www.wipo.int/pctdb/en/wo.jsp?WO=2008000430&IA=EP2007005622&DISPLAY=DESC

Bioactive Compounds From Cyanobacteria and Microalgae: An Overview
Critical Reviews in Biotechnology
Posted on: Sunday, 23 October 2005, 03:01 CDT

By Singh, Sawraj; Kate, Bhushan N; Banerjee, U C

ABSTRACT Cyanobacteria (blue-green algae) are photosynthetic prokaryotes used as food by humans. They have also been recognized as an excellent source of vitamins and proteins and as such are found in health food stores throughout the world. They are also reported to be a source of fine chemicals, renewable fuel and bioactive compounds. This potential is being realized as data from research in the areas of the physiology and chemistry of these organisms are gathered and the knowledge of cyanobacterial genetics and genetic engineering increased. Their role as antiviral, anti- tumour, antibacterial, anti-HIV and a food additive have been well established. The production of cyanobacteria in artificial and natural environments has been fully exploited. In this review the use of cyanobacteria and microalgae, production processes and biosynthesis of pigments, colorants and certain bioactive compounds are discussed in detail. The genetic manipulation of cyanobacteria and microalgae to improve their quality are also described at length.
http://www.redorbit.com/news/science/281044/bioactive_compounds_from_cyanobacteria_and_microalgae_an_overview/

Effect of a Klamath algae product ("AFA-B12") on blood levels of vitamin B12 and homocysteine in vegan subjects: a pilot study.
Int J Vitam Nutr Res. 2009 Mar;79(2):117-23.
...Compared to the control period, in the intervention period participants improved their vitamin B12 status, significantly reducing Hcy blood concentration (p=0.003). In conclusion, the Klamath algae product AFA-B12 appears to be, in a preliminary study, an adequate and reliable source of vitamin B12 in humans.
PMID: 20108213 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20108213

When you take two capsules, the ingredients help to support the release of stem cells from the bone marrow into the bloodstream. Through a natural process, those stem cells then travel to areas of the body where they are most needed... Adult stem cells are most abundantly found in bone marrow. Stem cells circulate and function to replace dysfunctional cells, thus fulfilling the natural process of maintaining optimal health. StemEnhance supports the release of adult stem cells from bone marrow into circulation...
StemTech HealthSciences of Klamath Falls, Oregon
http://www.stemtechhealth.com/

PatientsLikeMe.com
StemEnhance (blue-green algae) Treatment Report
http://www.patientslikeme.com/all/treatments/show/1948-stem-enhance?brand=t

Taxonomic re-evaluation of Aphanizomenon flos-aquae NH-5 based on morphology and 16S rRNA gene sequences
Renhui Li, Wayne W. Carmichael, Yongding Liu and Makoto M. Watanabe
Hydrobiologia
Volume 438, Numbers 1-3, 99-105, DOI: 10.1023/A:1004166029866

Abstract
The taxonomy of Aphanizomenon flos-aquae strain NH-5, a producer of cyanotoxins, was re-evaluated by comparison with six other Aphanizomenon strains using morphological characteristics and 16S rRNA gene sequences. Strain NH-5 was concluded to be improperly identified as Aph. flos-aquae based upon (1) lack of bundle formation in the trichomes, (2) location of akinetes next to heterocytes, (3) lower similarities (less than 97.5%) in the 16S rRNA gene sequences relative to Aph. flos-aquae strains, and (4) comparison within a phylogenetic tree constructed from 16S rRNA gene sequences. The Aphanizomenon strains investigated in this study are classified to four morphological groups as described by the classical taxonomy of Komárek & Kovácik (1989). This classification was supported from the phylogenetic results of 16S rRNA gene sequences. This study also discusses the generic boundaries between Aphanizomenon and Anabaena.
http://www.springerlink.com/content/p28521u04518l453/

Risk Assessment of Microcystin in Dietary Aphanizomenon flos-aquae
David J. Schaeffera, 1, Phyllis B. Malpasa, 2 and Larry L. Bartonb
Available online 2 April 2002.

Abstract

Aphanizomenon flos-aquae, a cyanobacterium that is marketed as a health food supplement, is harvested from natural blooms in Klamath Lake (Oregon) that are occasionally contaminated by Microcystis spp. Regulatory agencies in several countries are developing regulations to control the amount of microcystin in drinking water and other products, including products produced from A. flos-aquae. Regulation of microcystin (MC), a toxin produced by Microcystis spp. that is potentially present in natural culture of A. flos-aquae, should be based on studies in which a test species is exposed to the natural mixture of these cyanobacteria. A 1984 feeding trial to determine the effects of high dietary levels of A. flos-aquae on reproduction and development of mice is reanalyzed in light of recent analyses for microcystin-LR (MCLR) in the diets of those mice. Young adult mice consuming up to 333 µg MCLR/kg body weight (bw)/day exhibited no adverse effects on growth and reproduction, fetal development, and survival and organ weights of neonates. Based on a NOAEL of 333 µg MCLR/kg bw/day, a safety factor of 1000, consumption of 2 g/day of A. flos-aquae by a 60-kg adult, the safe level of MCLR as a contaminant of A. flos-aquae products is calculated to be 10.0 µg MCLR/g.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WDM-45GWF99-18&_user=10&_coverDate=09%2F30%2F1999&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=35e803c068e3d6b8704617e039ae6963&searchtype=a

11. Gentile JH. 1971. Blue green and green algal toxins, pp. 27-67 in vol. 7 of Microbial Toxins, Kadis S, Ciegler A, Ajl SJ, Eds., Academic Press, NY.

Phinney HK, Peek CA. 1961. Klamath Lake, an instance of natural enrichment. Trans. Sem. on Algae and Metropolitan Wastes. Robert A. Taft Sanitary Engineering Center, Cincinnati, OH.

For sale: Stem cell enhancers
Dietary supplement claims to boost circulating stem cells, but is it safe?
By Kerry Grens
The Scientist on "StemEnhance"
[Published 15th May 2007 02:49 PM GMT]
...And if the product does what it says, [stimulate the release of adult stem cells] it may not be safe, according to Frishman. One of the risks of taking a stem cell enhancer is that it could activate dormant cancer cells, he told The Scientist. There are other stem cell enhancing drugs that target particular cell types, such as granulocyte colony-stimulating factor, which elevates white blood cells after chemotherapy. "Here [with StemEnhance] you're giving a general stem cell booster," Frishman said. "Some people might have occult malignancies and all of a sudden you're giving them a stem cell booster.
http://sci.rutgers.edu/forum/archive/index.php/t-82032.html
http://sci.rutgers.edu/forum/showthread.php?t=82032

Mobilization of bone marrow stem cells with StemEnhance improves muscle regeneration in cardiotoxin-induced muscle injury.
Drapeau C, Antarr D, Ma H, Yang Z, Tang L, Hoffman RM, Schaeffer DJ.
Cell Cycle. 2010 May;9(9):1819-23. Epub 2010 May 17.

STEMTech HealthSciences, Inc., San Clemente, CA, USA. cdrapeau@stemtechmail.com
Abstract

Bone marrow-derived stem cells have the ability to migrate to sites of tissue damage and participate in tissue regeneration. The number of circulating stem cells has been shown to be a key parameter in this process. Therefore, stimulating the mobilization of bone marrow stem cells may accelerate tissue regeneration in various animal models of injury. In this study we investigated the effect of the bone marrow stem cells mobilizer StemEnhance (SE), a water-soluble extract of the cyanophyta Aphanizomenon flos-aquae (AFA), on hematopoietic recovery after myeloablation as well as recovery from cardiotoxin-induced injury of the anterior tibialis muscle in mice. Control and SE-treated female mice were irradiated, and then transplanted with GFP(+) bone marrow stem cells and allowed to recover. Immediately after transplant, animals were gavaged daily with 300 mg/kg of SE in PBS or a PBS control. After hematopoietic recovery (23 days), mice were injected with cardiotoxin in the anterior tibialis muscle. Five weeks later, the anterior tibialis muscles were analyzed for incorporation of GFP(+) bone marrow-derived cells using fluorescence imaging. SE significantly enhanced recovery from cardiotoxin-injury. However, StemEnhance did not affect the growth of the animal and did not affect hematopoietic recovery after myeloablation, when compared to control. This study suggests that inducing mobilization of stem cells from the bone marrow is a strategy for muscle regeneration.

PMID: 20404540 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20404540

Mobilization of human CD34+ CD133+ and CD34+ CD133(-) stem cells in vivo by consumption of an extract from Aphanizomenon flos-aquae--related to modulation of CXCR4 expression by an L-selectin ligand?

Jensen GS, Hart AN, Zaske LA, Drapeau C, Gupta N, Schaeffer DJ, Cruickshank JA.
Cardiovasc Revasc Med. 2007 Jul-Sep;8(3):189-202

Abstract

OBJECTIVE: The goal of this study was to evaluate effects on human stem cells in vitro and in vivo of an extract from the edible cyanobacterium Aphanizomenon flos-aquae (AFA) enriched for a novel ligand for human CD62L (L-selectin).

EXPERIMENTAL APPROACH: Ligands for CD62L provide a mechanism for stem cell mobilization in conjunction with down-regulation of the CXCR4 chemokine receptor for stromal derived factor 1. Affinity immunoprecipitation was used to identify a novel ligand for CD62L from a water extract from AFA. The effects of AFA water extract on CD62L binding and CXCR4 expression was tested in vitro using human bone marrow CD34+ cells and the two progenitor cell lines, KG1a and K562. A double-blind randomized crossover study involving 12 healthy subjects evaluated the effects of consumption on stem cell mobilization in vivo.

RESULTS: An AFA extract rich in the CD62L ligand reduced the fucoidan-mediated externalization of the CXCR4 chemokine receptor on bone marrow CD34+ cells by 30% and the CD62L+ CD34+ cell line KG1A by 50% but did not alter the CXCR4 expression levels on the CD34(-) cell line K562. A transient, 18% increase in numbers of circulating CD34+ stem cells maximized 1 hour after consumption (P<.0003). When 3 noncompliant volunteers were removed from analysis, the increase in CD34+ cells was 25% (P<.0001).

CONCLUSION: AFA water extract contains a novel ligand for CD62L. It modulates CXCR4 expression on CD34+ bone marrow cells in vitro and triggers the mobilization of CD34+ CD133+ and CD34+ CD133(-) cells in vivo.

PMID: 17765649 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/17765649

Consumption of Aphanizomenon flos-aquae has rapid effects on the circulation and function of immune cells in humans.
Drapeau, C. JANA 2000, 2, 50-58.
[NEED PUBMED CITATION]

Effects of blue-green algae extracts on the proliferation of human adult stem cells in vitro: a preliminary study.
Shytle DR, Tan J, Ehrhart J, Smith AJ, Sanberg CD, Sanberg PR, Anderson J, Bickford PC.
Department of Neurosurgery, USF, Tampa, FL, USA.
Med Sci Monit. 2010 Jan;16(1):BR1-5.

Abstract

BACKGROUND: Adult stem cells are known to have a reduced restorative capacity as we age and are more vulnerable to oxidative stress resulting in a reduced ability of the body to heal itself. We have previously reported that a proprietary nutraceutical formulation, NT-020, promotes proliferation of human hematopoietic stem cells in vitro and protects stem cells from oxidative stress when given chronically to mice in vivo. Because previous reports suggest that the blue green algae, Aphanizomenon flos-aquae (AFA) can modulate immune function in animals, we sought to investigate the effects of AFA on human stem cells in cultures.

MATERIAL/METHODS: Two AFA products were used for extraction: AFA whole (AFA-W) and AFA cellular concentrate (AFA-C). Water and ethanol extractions were performed to isolate active compounds for cell culture experiments. For cell proliferation analysis, human bone marrow cells or human CD34+ cells were cultured in 96 well plates and treated for 72 hours with various extracts. An MTT assay was used to estimate cell proliferation.

RESULTS: We report here that the addition of an ethanol extract of AFA-cellular concentrate further enhances the stem cell proliferative action of NT-020 when incubated with human adult bone marrow cells or human CD34+ hematopoietic progenitors in culture. Algae extracts alone had only moderate activity in these stem cell proliferation assays.

CONCLUSIONS: This preliminary study suggests that NT-020 plus the ethanol extract of AFA cellular concentrate may act to promote proliferation of human stem cell populations.

PMID: 20037479 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/20037479

Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.
Bachstetter AD, Jernberg J, Schlunk A, Vila JL, Hudson C, Cole MJ, Shytle RD, Tan J, Sanberg PR, Sanberg CD, Borlongan C, Kaneko Y, Tajiri N, Gemma C, Bickford PC.
Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, Tampa, Florida, United States of America.
PLoS One. 2010 May 5;5(5):e10496.

Abstract

Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS). To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg). The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p.) and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020) of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected against the negative influence of TNFalpha to reduce neural stem cell proliferation. These results support the hypothesis that a diet enriched with spirulina and other nutraceuticals may help protect the stem/progenitor cells from insults.
PMID: 20463965 [PubMed - indexed for MEDLINE]PMCID: PMC2864748
http://www.ncbi.nlm.nih.gov/pubmed/20463965
Full text at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2864748/?tool=pubmed

NT-020, a Natural Therapeutic Approach to Optimize Spatial Memory Performance and Increase Neural Progenitor Cell Proliferation and Decrease Inflammation in the Aged Rat.
Acosta S, Jernberg J, Sanberg CD, Sanberg PR, Small BJ, Gemma C, Bickford PC.
1 Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair and Department of Molecular Pharmacology and Physiology, University of South Florida College of Medicine , USFHealth, Tampa, Florida.
Rejuvenation Res. 2010 Jun 29. [Epub ahead of print]

Abstract

Abstract The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche.

PMID: 20586644 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/20586644

Dietary supplementation exerts neuroprotective effects in ischemic stroke model.
Yasuhara T, Hara K, Maki M, Masuda T, Sanberg CD, Sanberg PR, Bickford PC, Borlongan CV.
Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912, USA. cborlongan@mail.mcg.edu
Rejuvenation Res. 2008 Feb;11(1):201-14.

Abstract

This study examined whether dietary supplementation can be used to protect against ischemic stroke. Two groups of adult male Sprague-Dawley rats initially received NT-020, a proprietary formulation of blueberry, green tea, Vitamin D3, and carnosine (n = 8), or vehicle (n = 7). Dosing for NT-020 and vehicle consisted of daily oral administration (using a gavage) over a 2-week period. On day 14 following the last drug treatment, all animals underwent the stroke surgery using the transient 1-hour suture occlusion of middle cerebral artery (MCAo). To reveal the functional effects of NT-020, animals were subjected to established behavioral tests just prior to stroke surgery and again on day 14 post-stroke. ANOVA revealed significant treatment effects (p < 0.05), characterized by reductions of 11.8% and 24.4% in motor asymmetry and neurologic dysfunction, respectively, in NT-020-treated stroke animals compared to vehicle-treated stroke animals. Evaluation of cerebral infarction revealed a significant 75% decrement in mean glial scar area in the ischemic striatum of NT-020-treated stroke animals compared to that of vehicle-treated stroke animals (p < 0.0005). Quantitative analysis of subventricular zone's cell proliferative activity revealed at least a one-fold increment in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0005). Similarly, quantitative analysis of BrdU labeling in the ischemic striatal penumbra revealed at least a three-fold increase in the number of BrdU-positive cells in the NT-020-treated stroke brains compared to vehicle-treated stroke brains (p < 0.0001). In addition, widespread double labeling of cells with BrdU and doublecortin was detected in NT-020-treated stroke brains (intact side 17% and ischemic side 75%), which was significantly higher than those seen in vehicle-treated stroke brains (intact side 5% and ischemic side 13%) (p < 0.05). In contrast, only a small number of cells in NT-020-treated stroke brains double labeled with BrdU and GFAP (intact side 1% and ischemic side 2%), which was significantly lower than those vehicle-treated stroke brains (intact side 18% and ischemic side 35%) (p < 0.0001). Endogenous neurogenic factors were also significantly upregulated in the ischemic brains of NT-020-treated stroke animals. These data demonstrate the remarkable neuroprotective effects of NT-020 when given prior to stroke, possibly acting via its neurogenic potential.

PMID: 18260778 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/18260778

Stem Naturals increases adult stem cells and stem cell release for optimum health benefits. The Stem Naturals Stem cell Activator formula insures to create a better road to absorption by getting rid of toxins that block nutritional benefits in your body.  Stem Naturals Stem cell Activator formula will enable the effective use of nutrients in your body to the greatest degree possible.
http://www.bluegreenfoods.com/shop/proddetail.php?prod=Stem-Cell-Activator

M I C R O A L G A E
First & Finest Superfood

by Gabriel Cousens, M.D.

(Note: the following article appeared in Body Mind Spirit Magazine in May 1995...

Because of these brain-enhancing qualities, I became interested in exploring the effect of AFA on Alzheimer's disease. In my preliminary research, which was published in the Journal of Orthomolecular Medicine in the 1985 Winter / Spring Issue, I reported positive effects in both of two closely followed clients. Each had been diagnosed with Alzheimer's disease at highly respected university medical centers.

One client was a 66-year-old woman with a seven-year history of Alzheimer's disease who, after six months, showed a partial reversal of her disease. Her response to the AFA seemed to level off after six months and no further improvement was noted. The second case involved a 64-year-old lawyer who had suffered with Alzheimer's for three years. He seemed to be going downhill rapidly. After one month on high doses of AFA his degenerative process seemed to be arrested and he remained in this stabilized condition for three more years -- until his wife discovered that spirulina was cheaper than AFA and began to give him spirulina instead. Once off the AFA his condition began to deteriorate. The degeneration was slowed down when she put him back on the AFA. This unintended experiment highlights the difference in effect between AFA and spirulina.

These two cases do not prove that AFA cures Alzheimer's disease, but suggest it may be possible to temporarily halt the progression of the disease, to partially reverse or even help prevent it. It would take a comprehensive study to make any definitive statements about its effect on Alzheimer's and, as of yet, no study has been done...
http://www.algae-world.com/algae40.html

Colostrinin™ (also known as CLN, proline-rich polypeptides or PRP) is a naturally occurring proprietary mixture of proline-rich polypeptides derived from colostrum. The form used for human consumption is isolated from bovine colostrum by UK-based ReGen Therapeutics Plc...

A placebo-controlled clinical trial with Colostrinin in 106 Alzheimer’s sufferers over 30 weeks was completed in 2002 and the results appeared to demonstrate efficacy in a significant proportion of patients treated [8]. The results showed that approximately 40% of patients on Colostrinin were stabilized or improved after 15 weeks of therapy, based on an Analysis of Overall Response. 33% of patients continued to show stabilization or improvement after 30 weeks of treatment, although levels of benefit were slightly higher at the 15-week stage of the trial. The dosage regimen used for the trial was 100 micrograms of Colostrinin administered every second day for three weeks followed by a two-week period without Colostrinin.

A recent study by Froud et al. [9], published in the Journal of Alzheimer's Disease, demonstrated that Colostrinin significantly relieved amyloid-beta (Aß)-induced cytotoxicity, alleviated the effect of Aß-induced cytotoxicity and caused a significant reduction in the elevated levels of the antioxidant enzyme SOD1.

An in-vitro study completed in 2005 showed that Colostrinin can increase the lifespan of cells isolated from inbred mice predisposed to premature aging and death [10]. This study showed the impact of Colostrinin on the mitochondria of cells isolated from strains of senescence-prone (SAMP1) and senescence-resistant (SAMR1) mice. The data showed that cells from SAMP1 mice produce more reactive oxygen species (ROS), exhibit severe mitochondrial dysfunction, and have a decreased lifespan compared to the cells from SAMR1 mice. Addition of Colostrinin to SAMP1 cells significantly decreased ROS levels, normalized mitochondrial function and increased the lifespan to levels similar to those in SAMR1 cells. This in-vitro effect was followed up in actual mice as well.

Another study showed that Colostrinin induces neurite outgrowth of pheochromocytoma cells and inhibits beta amyloid-induced apoptosis [11]. The neurite outgrowth caused by Colostrinin appears to activate signaling pathways common to cell proliferation and differentiation, and to mediate a wide spectrum of activities that are similar to those of hormones and known nerve growth factors. These findings would seem to suggest that Colostrinin treatment may control the expression of genes that are involved in the development, maintenance, and regeneration of neurons in the central nervous system, and thus may also explain the improvements observed in Alzheimer's patients with mild-to-moderate dementia during treatment with Colostrinin.

... An in-vitro study completed in 2005 showed that Colostrinin can increase the lifespan of cells isolated from inbred mice predisposed to premature aging and death [10]. This study showed the impact of Colostrinin on the mitochondria of cells isolated from strains of senescence-prone (SAMP1) and senescence-resistant (SAMR1) mice. The data showed that cells from SAMP1 mice produce more reactive oxygen species (ROS), exhibit severe mitochondrial dysfunction, and have a decreased lifespan compared to the cells from SAMR1 mice. Addition of Colostrinin to SAMP1 cells significantly decreased ROS levels, normalized mitochondrial function and increased the lifespan to levels similar to those in SAMR1 cells. This in-vitro effect was followed up in actual mice as well.
http://en.wikipedia.org/wiki/Colostrinin

Cognisure:
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/8831053392

Colostrinin:
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/324306253

Colostrinin proline-rich polypeptide complex from ovine colostrum--a long-term study of its efficacy in Alzheimer's disease.
Leszek J, Inglot AD, Janusz M, Byczkiewicz F, Kiejna A, Georgiades J, Lisowski J.
Department of Psychiatry, Medical University of Wrocław, Wrocław, Poland. jleszek@psych.am.wroc.pl
Med Sci Monit. 2002 Oct;8(10):PI93-6.

Abstract

BACKGROUND: Colostrinin, a proline-rich polypeptide complex (PRP) isolated from ovine colostrum, with immunoregulatory and procognitive properties, has shown positive effects in the treatment of Alzheimer's disease (AD). The aim of the present study was to evaluate the effects of long-term Colostrinin treatment of AD patients.

MATERIAL/METHODS: The patients were taking Colostrinin tablets (containing 100 mg of PRP complex) every other day for three weeks, followed by a 2-week hiatus to avoid the development of hyporeactivity. This mode of application, '3+2 weeks,' was used consistently throughout the trial. The efficacy of treatment was assessed by the MMSE scale, and each patient was evaluated at 4-month intervals. 33 patients were treated for 16 months. However, 13 patients from this group had already been treated with Colostrinin for 12 months during placebo-controlled studies, and thus participated in the trial for a total of 28 months.

RESULTS: The results we obtained showed that Colostrinin induced slight but statistically significant improvement or stabilization of the health status of the patients in the trial. The adverse reactions observed, if any, were remarkably mild, including anxiety, logorrhea, and insomnia, and subsided spontaneously within a short period of time (3-4 days).

CONCLUSIONS: Colostrinin is a very promising preparation which can be used to retard the development of AD.
http://www.ncbi.nlm.nih.gov/pubmed/12388930

Full text: http://www.medscimonit.com/fulltxt.php?ICID=4860

When Sleep Apnea Masquerades as Dementia
New York Times October 6, 2010
By PAULA SPAN
...obstructive sleep apnea — nightlong interruptions in breathing that reduce oxygen flow to the brain and prevent deep sleep. The interruptions can happen 10 or more times an hour and are quite common in older adults, exacerbating — or sometimes mimicking — dementia symptoms.

Treated with a C.P.A.P. machine — the acronym stands for continuous positive airway pressure, a therapy that involves wearing a mask over the nose and/or mouth during sleep — the woman rapidly improved. Her scores on neuropsychological tests eventually climbed back into the normal range. A year later, Dr. Petersen said, “I can’t find any abnormalities.”

Most of the time, cognitive problems won’t evaporate when seniors are treated for sleep apnea. But researchers find that with C.P.A.P., many older patients see marked improvement...
http://newoldage.blogs.nytimes.com/2010/10/06/when-sleep-apnea-masquerades-as-dementia/

Rheumatoid Arthritis Signaling Protein Reverses Alzheimer's Disease in Mouse Model
ScienceDaily (Aug. 23, 2010)
A signaling protein released during rheumatoid arthritis dramatically reduced Alzheimer's disease pathology and reversed the memory impairment of mice bred to develop symptoms of the neurodegenerative disease, a new study by the University of South Florida reports. Researchers found that the protein, GM-CSF, likely stimulates the body's natural scavenger cells to attack and remove Alzheimer's amyloid deposits in the brain. The study appears online in the Journal of Alzheimer's Disease. People with rheumatoid arthritis, a chronic disease leading to inflammation of joints and surrounding tissue, are less likely than those without arthritis to develop Alzheimer's. While it was commonly assumed that non-steroidal anti-inflammatory drugs may help prevent onset and progression of Alzheimer's disease, recent NSAID clinical trials proved unsuccessful for patients with Alzheimer's...
http://www.sciencedaily.com/releases/2010/08/100822211549.htm

Can anti-inflammatory drugs prevent Alzheimer’s disease?

One of the hallmarks of Alzheimer’s disease is inflammation in the brain, but whether it is a cause or an effect of the disease is not yet known. Epidemiologic evidence strongly suggests that anti-inflammatory agents, such as prednisone (a steroid) and the popular pain relievers known as non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and indomethacin are associated with a decreased risk of Alzheimer’s. Studies in animal models of Alzheimer’s suggest that an NSAID can limit plaque production in the mouse brain.

However, results of a study that compared the effects of prednisone versus a placebo (inactive pill) on people who had been diagnosed with Alzheimer’s found no difference in cognitive decline between the prednisone and placebo treatment groups. Thus, a low-dose regimen of prednisone does not seem to be useful in treating Alzheimer’s disease.

A report in the Journal of the American Medical Association found that two popular NSAIDs, naproxen (Aleve) and the prescription arthritis painkiller rofecoxib (Vioxx), did nothing to slow the progression of Alzheimer’s disease in people with mild to moderate decline. However, previous studies suggest that NSAIDs may help to prevent Alzhiemer’s disease.

There is evidence that these or related drugs can reduce the risk of developing the illness in the first place if given to people before the onset of symptoms. A large study that followed nearly 7,000 patients for an average of 6.8 years found that people who did not use NSAIDs had a nearly five times greater risk of developing the disease than those who used NSAIDs long-term (24 months or more of cumulative use). People who used NSAIDs for more than one but less than 24 months also had a decreased risk of developing Alzheimer’s. The risk did not vary according to age. These data provide perhaps the most convincing evidence to date that NSAIDs may be useful in the prevention of Alzheimer’s disease.

However, a large government study designed to test whether the anti-inflammatory drugs naproxen (an NSAID sold as Aleve) or Celebrex (a pain reliever related to Vioxx and known as a COX-2 inhibitor) was halted after researchers noted that these drugs may cause an increased risk of heart attacks and strokes. Researchers had long known that NSAIDs are associated with gastrointestinal problems, including bleeding ulcers and with kidney problems, but the heart complications present an additional potential danger. These drugs must be used with caution, and only under a doctor’s supervision.

More research is needed on the safety of the various anti-inflammatory drugs and their possible benefits for treating or preventing Alzheimer’s disease. It is possible that those with Alzheimer’s who take different anti-inflammatories or different doses might show benefits. More studies of NSAIDs are under way. Drugs that work against toxic amyloid, the substance that contributes to plaque buildup and that is thought to be key to Alzheimer’s, are also under investigation.

Sources:
Use of Non-Steroidal Anti-Inflammatory Drugs Suspended in Large Alzheimer’s Disease Prevention Trial. National Institutes of Health, http://www.nih.gov/news/pr/dec2004/od-20.htm
http://www.alzinfo.org/research/alzheimers-research-aimed-at-prevention

Nicotine Could Play Role in Alzheimer's Disease Therapy, Neuroscientists Discover

ScienceDaily (Oct. 13, 2010) — A team of neuroscientists has discovered important new information in the search for an effective treatment for Alzheimer's disease, the debilitating neurological disorder that afflicts more than 5.3 million Americans and is the sixth-leading cause of death in the United States. Hey-Kyoung Lee, associate professor in the University of Maryland Department of Biology, and her research team have shown that they may be able to eliminate debilitating side effects caused by a promising Alzheimer's drug by stimulating the brain's nicotine receptors.
http://www.sciencedaily.com/releases/2010/10/101013095331.htm

Saffron (pronounced /ˈsæfrɒn/) is a spice derived from the flower of the saffron crocus (Crocus sativus), a species of crocus in the Iridaceae. A C. sativus flower bears three stigmas, each the distal end of a carpel. Together with their styles—stalks connecting stigmas to their host plant—stigmas are dried and used in cooking as a seasoning and colouring agent. Saffron, long the world's most expensive spice by weight,[1][2] is native to Southwest Asia.[2][3]

Saffron's bitter taste and an iodoform- or hay-like fragrance result from the chemicals picrocrocin and safranal.[4][5] A carotenoid dye, crocin, allows saffron to impart a rich golden-yellow hue to dishes and textiles...
http://en.wikipedia.org/wiki/Saffron

Eating Saffron Could Lower Alzheimer's Risk
FoxNews.com Published November 02, 2010
By Chris Kilham

Recent studies show that saffron may play a valuable role in delaying mental decline in cases of Alzheimer’s disease.

But before I get to those studies, here's a little background on saffron: The world’s most expensive spice by weight, saffron is the stigmas of a variety of crocus flower. Stigmas are thread-like female reproductive parts of the flower. In the case of saffron, the stigmas are brilliant red or orange, and have been used since antiquity in cooking and in medicinal preparations. The spice was popular in ancient Egypt and in Rome, and was cultivated in both places. Originating from central Asia, saffron is commercially cultivated primarily in the Mediterranean region. This is a highly labor-intensive spice, typically requiring more than 100,000 flowers to yield one kilogram (2.2 pounds) of dried saffron spice... We have seen such activity with another spice, turmeric, which is also a yellow dye. In studies of a primary ingredient in turmeric called curcumin, researchers have found that the development of beta-amyloid plaque can be inhibited...
http://www.foxnews.com/health/2010/11/02/eating-saffron-lower-alzheimers-risk/

Saffron in the treatment of patients with mild to moderate Alzheimer's disease: a 16-week, randomized and placebo-controlled trial.

Akhondzadeh S, Sabet MS, Harirchian MH, Togha M, Cheraghmakani H, Razeghi S, Hejazi SSh, Yousefi MH, Alimardani R, Jamshidi A, Zare F, Moradi A.

Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran Institute of Medicinal Plants (ACECR), Department of Neurology, Tehran, Iran. s.akhond@neda.net

Abstract

WHAT IS KNOWN: Herbal medicines have been used in the treatment of behavioural and psychological symptoms of dementia but with variable response. Crocus sativus (saffron) may inhibit the aggregation and deposition of amyloid β in the human brain and may therefore be useful in Alzheimer's disease (AD).

OBJECTIVE: The goal of this study was to assess the efficacy of saffron in the treatment of mild to moderate AD.

METHODS: Forty-six patients with probable AD were screened for a 16-week, double-blind study of parallel groups of patients with mild to moderate AD. The psychometric measures, which included AD assessment scale-cognitive subscale (ADAS-cog), and clinical dementia rating scale-sums of boxes, were performed to monitor the global cognitive and clinical profiles of the patients. Patients were randomly assigned to receive capsule saffron 30 mg/day (15 mg twice per day) (Group A) or capsule placebo (two capsules per day) for a 16-week study.

RESULTS: After 16 weeks, saffron produced a significantly better outcome on cognitive function than placebo (ADAS-cog: F=4·12, d.f.=1, P=0·04; CDR: F=4·12, d.f.=1, P=0·04). There were no significant differences in the two groups in terms of observed adverse events.

WHAT IS NEW AND CONCLUSION: This double-blind, placebo-controlled study suggests that at least in the short-term, saffron is both safe and effective in mild to moderate AD. Larger confirmatory randomized controlled trials are called for.

J Clin Pharm Ther. 2010 Oct;35(5):581-8. doi: 10.1111/j.1365-2710.2009.01133.x. PMID: 20831681
http://www.ncbi.nlm.nih.gov/pubmed/20831681

A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease.

http://www.ncbi.nlm.nih.gov/pubmed/19838862

Can Leukine Stop or Slow Down Alzheimer's Disease?
Alzheimer's Reading Room
Monday, August 23, 2010
By Bob DeMarco

A signaling protein released during rheumatoid arthritis dramatically reduced Alzheimer's disease pathology and reversed the memory impairment of mice bred to develop symptoms of the neurodegenerative disease, a new study by the University of South Florida reports.

Researchers found that the protein, GM-CSF (Leukine), likely stimulates the body's natural scavenger cells to attack and remove Alzheimer's amyloid deposits in the brain.

The study appeared online in the Journal of Alzheimer's Disease.

People with rheumatoid arthritis, a chronic disease leading to inflammation of joints and surrounding tissue, are less likely than those without arthritis to develop Alzheimer's. While it was commonly assumed that non-steroidal anti-inflammatory drugs may help prevent onset and progression of Alzheimer's disease, recent NSAID clinical trials proved unsuccessful for patients with Alzheimer's...

"Moreover, the recombinant human form of GM-CSF (Leukine®) is already approved by the FDA and has been used for years to treat certain cancer patients who need to generate more immune cells," Dr. Potter said. "Our study, along with the drug's track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer's disease."

http://www.alzheimersreadingroom.com/2010/08/can-leukine-stop-or-slow-down.html

Protein linked to arthritis could help treat Alzheimer's
The Scotsman
Published Date: 23 August 2010
By Lyndsay Moss
http://thescotsman.scotsman.com/news/Protein-linked-to-arthritis-could.6488309.jp?articlepage=1

In Parkinson's Disease, Brain Cells Abandon Mitochondria

ScienceDaily (Oct. 8, 2010) — In a study that sheds new light on the causes of Parkinson's disease, researchers report that brain cells in Parkinson's patients abandon their energy-producing machinery, the mitochondria. A shutdown in fuel can have devastating effects on brain cells, which consume roughly 20 percent of the body's energy despite making up only 2 percent of body weight... researchers, now show that a root cause of Parkinson's disease may lie in 10 gene sets related to energy production that spur neurons in the brain to "divorce" their mitochondria and related energy-producing pathways..."The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson's disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria,"... FDA-approved medications [Actos, CoQ10] that activate that PGC-1alpha are already available for widespread diseases like diabetes. These medications may jumpstart the development of new Parkinson's drugs; instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain. "As we wrap up our first year of publishing the journal, the new study from Zheng et al. exemplifies the goal of Science Translational Medicine, applying knowledge and technology from different fields-such as neuroscience, genomics and bioinformatics-to achieve new discoveries,"...
http://www.sciencedaily.com/releases/2010/10/101006151557.htm

Study: Brain energy crisis may spark Parkinson's
By LAURAN NEERGAARD, AP Medical Writer
Tuesday, November 2, 2010

...A diabetes drug named Actos is among the compounds known to activate part of that PGC-1alpha pathway, and Weill Cornell's Beal says it's poised for an initial small trial in Parkinson's. Separately, a nutrient named Coenzyme Q10 is believed important in mitochondrial energy production, and Beal is leading a study to see if high doses might help Parkinson's. Results are due in 2012...

In Parkinson's Disease, Brain Cells Abandon Mitochondria

ScienceDaily (Oct. 8, 2010) — In a study that sheds new light on the causes of Parkinson's disease, researchers report that brain cells in Parkinson's patients abandon their energy-producing machinery, the mitochondria. A shutdown in fuel can have devastating effects on brain cells, which consume roughly 20 percent of the body's energy despite making up only 2 percent of body weight... researchers, now show that a root cause of Parkinson's disease may lie in 10 gene sets related to energy production that spur neurons in the brain to "divorce" their mitochondria and related energy-producing pathways..."The most exciting result from our study for me is the discovery of PGC-1alpha as a new therapeutic target for early intervention in Parkinson's disease. PGC-1alpha is a master switch that activates hundreds of mitochondrial genes, including many of those needed to maintain and repair the power plants in the mitochondria,"... FDA-approved medications [Actos, CoQ10] that activate that PGC-1alpha are already available for widespread diseases like diabetes. These medications may jumpstart the development of new Parkinson's drugs; instead of having to start from scratch, pharmaceutical companies may be able to dust off their drug libraries and find look-alike drugs capable of targeting PGC-1alpha in the brain. "As we wrap up our first year of publishing the journal, the new study from Zheng et al. exemplifies the goal of Science Translational Medicine, applying knowledge and technology from different fields-such as neuroscience, genomics and bioinformatics-to achieve new discoveries,"...
http://www.sciencedaily.com/releases/2010/10/101006151557.htm

Study: Brain energy crisis may spark Parkinson's
By LAURAN NEERGAARD, AP Medical Writer
Tuesday, November 2, 2010

...A diabetes drug named Actos is among the compounds known to activate part of that PGC-1alpha pathway, and Weill Cornell's Beal says it's poised for an initial small trial in Parkinson's. Separately, a nutrient named Coenzyme Q10 is believed important in mitochondrial energy production, and Beal is leading a study to see if high doses might help Parkinson's. Results are due in 2012...

http://www.sfgate.com/cgi-bin/article.cgi?f=/n/a/2010/11/01/national/w100153D54.DTL#ixzz146V9bQy7

How The Pathology Of Parkinson's Disease Spreads
ScienceDaily (July 29, 2009) — Accumulation of the synaptic protein alpha-synuclein, resulting in the formation of aggregates called Lewy bodies in the brain, is a hallmark of Parkinson's and other related neurodegenerative diseases. This pathology appears to spread throughout the brain as the disease progresses. Now, researchers at the University of California, San Diego School of Medicine and Konkuk University in Seoul, South Korea, have described how this mechanism works... "The discovery of cell-to-cell transmission of this protein may explain how alpha-synuclein aggregates can pass to new, healthy cells," said first author Paula Desplats, project scientist in UC San Diego's Department of Neurosciences. "We demonstrated how alpha-synuclein is taken up by neighboring cells, including grafted neuronal precursor cells, a mechanism that may cause Lewy bodies to spread to different brain structures."... In these studies, autopsies of deceased Parkinson's patients who had received implants of therapeutic fetal neurons 11 to 16 years prior revealed that alpha-synuclein had propagated to the transplanted neurons...
http://www.sciencedaily.com/releases/2009/07/090727191914.htm]

Diabetes Drug Could Work Against Alzheimer's, Animal Study Suggests

ScienceDaily (Nov. 24, 2010)
Metformin, a drug used in type 2-diabetes might have the potential to also act against Alzheimer's disease... The researchers have found out that the diabetes drug metformin counteracts alterations of the cell structure protein Tau in mice nerve cells. These alterations are a main cause of the Alzheimer's disease. Moreover, they uncovered the molecular mechanism of metformin in this process...  results have been published in the Proceedings of the National Academy of Sciences (Nov. 22, 2010)...
http://www.sciencedaily.com/releases/2010/11/101124114538.htm


Cocktail of cheap drugs 'can prevent Alzheimer's' and keep the brain healthy into old age
By Fiona Macrae
Last updated at 8:38 AM on 23rd November 2010

A cheap diabetes drug taken with a red wine ‘miracle pill’ could prevent millions from suffering the agony of Alzheimer’s. Costing only pennies a day, the two-in-one cocktail could keep the brain healthy into old age, stopping dementia developing in some cases and halting it in others, British doctors believe. With the pills already credited with a host of health-boosting qualities, including potentially extending life, the Dundee University breakthrough brings hope of a brighter future for millions... The latest breakthrough centres on drugs called metformin and resveratrol. Metformin has been safely used for more than 50 years to control blood sugar levels in age and obesity-related diabetes. Recent research suggests it has other benefits, including the ability to extend life. Resveratrol, the ‘miracle ingredient’ behind many of red wine’s health-boosting qualities, has also been hailed as an elixir of life, with experiments crediting it with warding off a host of ills, from old age to cancer.
http://www.dailymail.co.uk/health/article-1332185/Alzheimers-prevented-cocktail-cheap-drugs-including-metformin-resveratrol.html?printingPage=true

Diabetes Drug May Treat Alzheimer's Disease
November 25, 2010
David Goodhue - AHN News Reporter

Germany (AHN) - German scientists say a drug taken to treat type-2 diabetes may be effective against Alzheimer’s disease.

The researchers said the drug metformin counteracts alterations of the cell structure protein known as Tau in mice models. These cell structure changes are a significant cause of the development of Alzheimer’s, the researchers said in a statement.

The scientists were from the German Center for Neurodegenerative Disease, the University of Dundee and the Max-Planck-Institute for Molecular Genetices...
http://www.allheadlinenews.com/articles/7020635217?Diabetes%20Drug%20May%20Treat%20Alzheimer's%20Disease

Metformin in Amnestic Mild Cognitive Impairment (MCI)
This study is currently recruiting participants.
Verified by Columbia University, October 2010
First Received:          February 7, 2008   Last Updated: October 13, 2010   History of Changes
Sponsor:                 Columbia University
Collaborators:           Institute for the Study of Aging (ISOA)
                         National Institute on Aging (NIA)
Information provided by: Columbia University
ClinicalTrials.gov Identifier: NCT00620191
http://clinicaltrials.gov/ct2/show/NCT00620191?term=Metformin+Alzheimer's&rank=1

Risk factors of vitamin B(12) deficiency in patients receiving metformin.
Arch Intern Med. 2006 Oct 9;166(18):1975-9.
Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, Hong Kong.

Abstract

BACKGROUND: Identification of risk factors for metformin-related vitamin B(12) deficiency has major potential implications regarding the management of diabetes mellitus.

METHODS: We conducted a nested case-control study from a database in which the source population consisted of subjects who had levels of both serum vitamin B(12) and hemoglobin A(1c) checked in a central laboratory. We identified 155 cases of diabetes mellitus and vitamin B(12) deficiency secondary to metformin treatment. Another 310 controls were selected from the cohort who did not have vitamin B(12) deficiency while taking metformin.

RESULTS: A total of 155 patients with metformin-related vitamin B(12) deficiency (mean +/- SD serum vitamin B(12) concentration, 148.6 +/- 40.4 pg/mL [110 +/- 30 pmol/L]) were compared with 310 matched controls (466.1 +/- 330.4 pg/mL [344 +/- 244 pmol/L]). After adjusting for confounders, we found clinically important and statistically significant association of vitamin B(12) deficiency with dose and duration of metformin use. Each 1-g/d metformin dose increment conferred an odds ratio of 2.88 (95% confidence interval, 2.15-3.87) for developing vitamin B(12) deficiency (P<.001). Among those using metformin for 3 years or more, the adjusted odds ratio was 2.39 (95% confidence interval, 1.46-3.91) (P = .001) compared with those receiving metformin for less than 3 years. After exclusion of 113 subjects with borderline vitamin B(12) concentration, dose of metformin remained the strongest independent predictor of vitamin B(12) deficiency.

CONCLUSIONS: Our results indicate an increased risk of vitamin B(12) deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders. The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients.

PMID: 17030830 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/17030830
Free full article: http://archinte.ama-assn.org/cgi/content/full/166/18/1975
                   http://archinte.ama-assn.org/cgi/reprint/166/18/1975

The epothilones are a new class of cancer drugs. Like taxanes, they prevent cancer cells from dividing by interfering with tubulin, but in early trials epithilones have better efficacy and milder adverse effects than taxanes...
http://en.wikipedia.org/wiki/Epothilone_D

Novel study offers hope for new class of Alzheimer's drugs

Washington, Oct 19 (ANI): A new Penn study has discovered and tested in an animal model of Alzheimer's disease a class of drug that is able to enter the brain, where it stabilizes degenerating neurons and improves memory and learning.In the normal brain, the protein tau plays an important role in stabilizing structures called microtubules in nerve cells, which serve as tracks upon which cellular material is transported.

In Alzheimer's disease and related disorders, tau becomes insoluble and forms clumps in the brain. One consequence of these aggregates is a depletion of normal tau, resulting in destabilization of the microtubule tracks that are critical for proper nerve-cell function.

Senior authors Virginia M.-Y. Lee, director of the Center for Neurodegenerative Disease Research (CNDR), and John Trojanowski, director of the Institute on Aging and CNDR co-director, introduced the concept of using microtubule-stabilizing drugs over 15 years ago to counteract tangles of tau and compensate for the loss of normal tau function.

Kurt Brunden, director of Drug Discovery at CNDR and Bin Zhang, senior research investigator, are the first authors on this study from the University of Pennsylvania School of Medicineand the School of Arts and Sciences.

In 2005, the CNDR researchers showed that the anti-cancer drug paclitaxel could improve spinal cord nerve function in mice with tau tangles in their brains, after the drug was absorbed at nerve termini in muscle.

"However, paclitaxel and related drugs do not cross the blood-brain barrier," notes Brunden. "So we surveyed a number of additional microtubule-stabilizing agents and discovered that the epothilone class, and in particular epothilone D, readily entered and persisted in the brain."

"The positive effect of epothilone D on the function of axons and on cognition, without the onset of side-effects offers hope that this class of microtubule-stabilizing drugs could progress to testing in Alzheimer patients in the near future," said Lee.

"There are very few tau-focused drugs in clinical trials now for Alzheimer's disease. While we and others have urged that pharmaceutical companies should not put all of their eggs in one drug basket to ensure the highest likelihood of finding disease-modifying therapies for Alzheimer's, we hope this successful mouse study of a tau drug will encourage more pharmaceutical companies to pursue programs on tau-focused drug discovery," said Trojanowski.

The study has been published this week in the Journal of Neuroscienc. (ANI)
http://news.oneindia.in/2010/10/19/novelstudy-offers-hope-for-new-class-of-alzheimersdrugs.html

5-lipoxygenase protein modulates amyloid beta formation linked to Alzheimer's disease
18. November 2010 01:36

A protein known to exist in the brain for more than 30 years, called 5-lipoxygenase, has been found to play a regulatory role in the formation of the amyloid beta in the brain, the major component of plaques implicated in the development of Alzheimer's disease, according to researchers at Temple University's School of Medicine.

The researchers also found that inhibitors of this protein currently used to control asthma could possibly be used to prevent or treat Alzheimer's disease... "What we found was 5-lipoxygenase regulates and controls the amount of total amyloid beta produced in the brain. With aging, the more 5-lipoxygenase you have the more amyloid beta you're going to produce. This will translate into a higher risk to develop full Alzheimer's."... He said that there are several FDA-approved 5-lipoxygenase inhibitors currently being used for the treatment of asthma, and that the Temple researchers tested some of these inhibitors in the lab against the production of amyloid beat with initial positive results...
http://www.news-medical.net/news/20101118/5-lipoxygenase-protein-modulates-amyloid-beta-formation-linked-to-Alzheimers-disease.aspx

Asthma medication may have potential as Alzheimer's treatment
Posted November 23, 2010 11:17 AM to the Alzheimer Association message board
"Medications/Treatments for Alzheimer's and Other Related Dementias"
by Billstrailrunning

The potential exciting news is that asthma drugs have been to developed to block this enzyme for the treatment of asthma and are FDA-approved for this indication. Zileuton is the only drug in the US that actually may block this enzyme directly. This drug used to be taken every 6 hours, but now there is a 12 hours dose. The downside is this drug can interact with other drugs and may increase liver enzmes.
 
Other options might be Singulair or Accolate which are drugs that block leukotriene receptors.
 
The issue is what dose might be needed to get enough of these drugs past the blood-brain barrier to get a level in the central nervous system to have an effect. The standard dose might not do it...
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/7694060087?r=7694060087#7694060087

Posted November 28, 2010 10:59 PM
by Ranwah

Boswellia serrata plant contains several substances that are 5-LOX inhibitors, there is also an extract of the most active elements and it's under the name 5-loxin. Similar to curcumin Boswellia also has some bio-availability issues.
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/7694060087?r=1564035087#1564035087

Cat's claw...
http://www.umm.edu/altmed/articles/cats-claw-000229.htm

Cat's claw (Uncaria tomentosa or Una do Gato) is a medicinal herb from the Amazon River basin that is widely used for inflammatory disorders. Cat's claw contains gluco indole alkaloids. This herb is promoted as having anti-cancer, anti-inflammatory, and for arthritis. In the traditional Peruvian medicine, hot aqueous extracts have been used for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. What does the research say?...
http://www.raysahelian.com/catsclaw.html

How to Use Cat's Claw to Treat Alzheimer's
Because some scientific studies suggest that cat's claw can stop the beta-amyloid plaques that cause Alzheimer's disease from forming in the brain, some people use it to treat and prevent the condition. Preliminary findings suggest that cat's claw may be an effective supplementary method for managing Alzheimer's disease and preventing the condition from worsening...
http://www.ehow.com/how_2119599_use-cats-claw-treat-alzheimers.html

Samento is a form of cat’s claw from the Peruvian jungle that is superior to typical forms. The beneficial effects of most cat’s claw preparations are blunted by the presence of TOA (tetracyclic oxindole alkaloids), which inhibit the real active agents, called POA (pentacyclic oxindole alkaloids). The latter, more favorable compounds are known to modulate and up-regulate the immune system. Many commercially available cat’s claw preparations contain up to 80 percent TOA. As little as one percent TOA can reduce POA effectiveness up to 80 percent. In addition, the specific species of TOA-free cat’s claw contains considerable quantities of quinovic acid glycosides. These compounds are what the latest generation of quinolone antibiotics (such as Cipro) are based on. The natural compounds provide safe and significant direct antimicrobial effects on Lyme disease...

Three companies currently market the improved cat’s claw. Allergy Research Group/Nutricology, which also distributes artemisinin, can be reached at 800-545-9960 or www.nutricology.com. Ask for Prima Una de Gato. Nutramedix’s product is called Samento Plus, and is available by calling 561-745-2917 or on the web site: www.nutramedix.com. Farmacopia also carries the product (www.farmacopia.net or 800-896-1484). I don’t recommend any other commercially available cat’s claw at this time because of the likelihood of TOA content.
http://www.medical-library.net/content/view/454/45/

SAMENTO is a very rare form of the Peruvian medicinal plant called Cat’s Claw - Uncaria tomentosa...
Unlike traditional Cat’s Claw products, SAMENTO does not contain a group of chemical antagonists called tetracyclic oxindole alkaloids (TOAs) that act upon the central nervous system and greatly inhibit its effectiveness. SAMENTO contains a standardized amount of pentacyclic oxindole alkaloids (POAs) that act on the cellular immune system and demonstrate powerful immune system modulating properties. According to research conducted in Austria, traditional Cat’s Claw products may contain as much as 80% TOAs, and as little as 1% TOAs can cause a 30% reduction in immune system modulating properties that POAs provide. This may explain why large dosages, at times far exceeding 20,000 mg per day, of traditional Cat’s Claw containing TOAs are required to obtain some results in treating the previously mentioned immune system related conditions... The Austrian scientist Klaus Keplinger discovered as early as in the 1970s that there was such a TOA-free Cat’s Claw, but it is so rare in nature that Keplinger managed to find in the Peruvian rainforest only separate specimens.
http://www.samento.com.ec/sciencelib/4sam/Sambook_healthfor.htm

Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaB.
J Ethnopharmacol. 2010 Feb 17;127(3):685-93. Epub 2009 Dec 6.
Allen-Hall L, Arnason JT, Cano P, Lafrenie RM.

Laurentian University, Biomolecular Science, Sudbury Regional Hospital, Sudbury, Ontario, Canada.
Abstract

AIM OF THE STUDY: Uncaria tomentosa, commonly known as Cat's Claw or Uña de gato, is a medicinal plant that has been shown to have effective anti-inflammatory activities. We have previously shown that treatment of monocyte-like THP-1 cells with Uncaria tomentosa inhibits the production of the pro-inflammatory cytokine TNF-alpha while augmenting the production of IL-1beta. Since TNF-alpha and IL-1beta are usually regulated similarly and share a number of common promoter elements, including NF-kappaB and AP-1, the ability of Uncaria tomentosa to differentially regulate these inflammatory cytokines is of particular interest.

MATERIALS AND METHODS: To determine the mechanism of action of Uncaria tomentosa, we investigated the effects of specific inhibitors of NF-kappaB on cellular responses including transcription factor activation using TransAM assays, the expression of cytokines as measured by ELISA, and cell survival as measured by changes in cell number following treatment.

RESULTS: Treatment with Uncaria tomentosa inhibited the LPS-dependent activation of specific NF-kappaB and AP-1 components. In addition, treatment with Uncaria tomentosa enhanced cell death when NF-kappaB was inhibited. The ability of Uncaria tomentosa to inhibit TNF-alpha production was diminished when NF-kappaB activation was prevented by drugs that mask NF-kappaB subunit nuclear localization signals, while IL-1beta expression was unchanged.

CONCLUSIONS: These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-kappaB-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-alpha therapies.
Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

PMID: 19995599 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19995599


Treatment of THP-1 cells with Uncaria tomentosa extracts differentially regulates the expression if IL-1beta and TNF-alpha.
J Ethnopharmacol. 2007 Jan 19;109(2):312-7. Epub 2006 Aug 3.

Allen-Hall L, Cano P, Arnason JT, Rojas R, Lock O, Lafrenie RM.

Regional Cancer Program, Sudbury Regional Hospital, Sudbury, Ont, Canada.
Abstract

Uncaria tomentosa, commonly known as cat's claw, is a medicinal plant native to Peru, which has been used for decades in the treatment of various inflammatory disorders. Uncaria tomentosa can be used as an antioxidant, has anti-apoptotic properties, and can enhance DNA repair, however it is best know for its anti-inflammatory properties. Treatment with Uncaria tomentosa extracts inhibits the production of the pro-inflammatory cytokine, TNF-alpha, which is a critical mediator of the immune response. In this paper, we showed that treatment of THP-1 monocyte-like cells with Uncaria tomentosa extracts inhibited the MAP kinase signaling pathway and altered cytokine expression. Using ELISA assays, we showed that treatment with Uncaria tomentosa extracts augmented LPS-dependent expression of IL-1beta by 2.4-fold, while inhibiting the LPS-dependent expression of TNF-alpha by 5.5-fold. We also showed that treatment of LPS-stimulated THP-1 cells with Uncaria tomentosa extracts blocked ERK1/2 and MEK1/2 phosphorylation in a dose-dependent manner. These data demonstrate that treatment of THP-1 cells with Uncaria tomentosa extracts has opposite effects on IL-1beta and TNF-alpha secretion, and that these changes may involve effects on the MAP kinase pathway.

PMID: 16959454 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16959454


Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators.
Altern Med Rev. 2006 Jun;11(2):128-50.
Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M.

Clinical Division, Department of Herbal Medicine, Tai Sophia Institute, 7750 Montpelier Road, Laurel, MD 20723, USA. spelman123@earthlink.net.
Abstract

Modulation of cytokine secretion may offer novel approaches in the treatment of a variety of diseases. One strategy in the modulation of cytokine expression may be through the use of herbal medicines. A class of herbal medicines, known as immunomodulators, alters the activity of immune function through the dynamic regulation of informational molecules such as cytokines. This may offer an explanation of the effects of herbs on the immune system and other tissues. For this informal review, the authors surveyed the primary literature on medicinal plants and their effects on cytokine expression, taking special care to analyze research that utilized the multi-component extracts equivalent to or similar to what are used in traditional medicine, clinical phytotherapy, or in the marketplace.

METHODOLOGY: MEDLINE, EBSCO, and BIOSIS were used to identify research on botanical medicines, in whole or standardized form, that act on cytokine activity through different models, i.e., in vivo (human and animal), ex vivo, or in vitro.

RESULTS: Many medicinal plant extracts had effects on at least one cytokine. The most frequently studied cytokines were IL-1, IL-6, TNF, and IFN. Acalypha wilkesiana, Acanthopanax gracilistylus, Allium sativum, Ananus comosus, Cissampelos sympodialis, Coriolus versicolor, Curcuma longa, Echinacea purpurea, Grifola frondosa, Harpagophytum procumbens, Panax ginseng, Polygala tenuifolia, Poria cocos, Silybum marianum, Smilax glabra, Tinospora cordifolia, Uncaria tomentosa, and Withania somnifera demonstrate modulation of multiple cytokines.

CONCLUSION: The in vitro and in vivo research demonstrates that the reviewed botanical medicines modulate the secretion of multiple cytokines. The reported therapeutic success of these plants by traditional cultures and modern clinicians may be partially due to their effects on cytokines. Phytotherapy offers a potential therapeutic modality for the treatment of many differing conditions involving cytokines. Given the activity demonstrated by many of the reviewed herbal medicines and the increasing awareness of the broad-spectrum effects of cytokines on autoimmune conditions and chronic degenerative processes, further study of phytotherapy for cytokine-related diseases and syndromes is warranted.

PMID: 16813462 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/16813462
Full text: http://www.ncbi.nlm.nih.gov/pubmed/16813462

Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects.
Semin Arthritis Rheum. 2005 Jun;34(6):773-84.
Setty AR, Sigal LH.

Massachusetts General Hospital, Department of Rheumatology, Boston, USA.
Abstract

OBJECTIVE: To review the literature on herbal preparations commonly utilized in the treatment of rheumatic indications.

METHODS: Search of MEDLINE (PubMed) was performed using both the scientific and the common names of herbs. Relevant articles in English were collected from PubMed and reviewed.

RESULTS: This review summarizes the efficacy and toxicities of herbal remedies used in complementary and alternative medical (CAM) therapies for rheumatologic conditions, by elucidating the immune pathways through which these preparations have antiinflammatory and/or immunomodulatory activity and providing a scientific basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced pro-IL-1beta gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but not for Sjogrens disease. The antiinflammatory actions of Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it may have a role in treating low back pain. While in vitro experiments with Tanacetum parthenium found inhibition of the expression of intercellular adhesion molecule-1, tumor necrosis factor alpha (TNF-alpha), interferon-gamma, IkappaB kinase, and a decrease in T-cell adhesion, to date human studies have not proven it useful in the treatment of RA. Current experience with Tripterygium wilfordii Hook F, Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while Urtica diocia and willow bark extract are effective for osteoarthritis. T. wilfordii Hook F extract inhibits the production of cytokines and other mediators from mononuclear phagocytes by blocking the up-regulation of a number of proinflammatory genes, including TNF-alpha, cyclooxygenase 2 (COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both decrease the production of TNF-alpha. At present there are no human studies on Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF-alpha, prostaglandin, and leukotriene synthesis and at present has limited efficacy in the treatment of osteoarthritis.

CONCLUSIONS: Investigation of the mechanism and potential uses of CAM therapies is still in its infancy and many studies done to date are scientifically flawed. Further systematic and scientific inquiry into this topic is necessary to validate or refute the clinical claims made for CAM therapies. An understanding of the mechanism of action of CAM therapies allows physicians to counsel effectively on their proper and improper use, prevent adverse drug-drug interactions, and anticipate or appreciate toxicities.

RELEVANCE: The use of CAM therapies is widespread among patients, including those with rheumatic diseases. Herbal medications are often utilized with little to no physician guidance or knowledge. An appreciation of this information will help physicians to counsel patients concerning the utility and toxicities of CAM therapies. An understanding and elucidation of the mechanisms by which CAM therapies may be efficacious can be instrumental in discovering new molecular targets in the treatment of diseases.

PMID: 15942912 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/15942912


Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity.
Phytochemistry. 2005 Jan;66(1):89-98.
Gonçalves C, Dinis T, Batista MT.

Abstract

Decoctions prepared from the bark of Uncaria tomentosa (cat's claw) are widely used in the traditional Peruvian medicine for the treatment of several diseases, in particular as a potent anti-inflammatory agent. Therefore, the main purpose of this study was to determine if the well-known anti-inflammatory activity of cat's claw decoction was related with its reactivity with the oxidant species generated in the inflammatory process and to establish a relationship between such antioxidant ability and its phenolic composition. We observed that the decoction prepared according to the traditional Peruvian medicine presented a potent radical scavenger activity, as suggested by its high capacity to reduce the free radical diphenylpicrylhydrazyl, and by its reaction with superoxide anion, peroxyl and hydroxyl radicals as well as with the oxidant species, hydrogen peroxide and hypochlorous acid. It also protected membrane lipids against peroxidation induced by the iron/ascorbate system, as evaluated by the formation of thiobarbituric acid-reactive substances (TBARs). The decoction phenolic profile was established by chromatographic analysis (HPLC/DAD and TLC) revealing essentially the presence of proanthocyanidins (oligomeric procyanidins) and phenolic acids, mainly caffeic acid. Thus, our results provide evidence for an antioxidant mechanism underlying the anti-inflammatory activity of cat's claw and support some of the biological effects of proanthocyanidins, more exactly its antioxidant and radical scavenging activities.

PMID: 15649515 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/15649515


Cat's claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.
Free Radic Biol Med. 2000 Jul 1;29(1):71-8.
Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ.

Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. sandovm@mail.amc.edu
Abstract

Cat's claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat's claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat's claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat's claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat's claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat's claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat's claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis.

PMID: 10962207 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/10962207

Potential Risks of Anti-Tumor Necrosis Factor Therapy for People with MS

May 26, 2003-We have received a number of questions from people about medications that block Tumor Necrosis Factor alpha (TNF alpha). TNF, a substance that is part of the immune system, plays a role in the inflammation that occurs in a variety of autoimmune diseases. It has additional functions in the immune system that are still unclear.1 While medications that block TNF have been found to be useful in other autoimmune diseases, they should not be used in the treatment of multiple sclerosis (MS) because they may actually worsen the disease. Cases of new onset multiple sclerosis, optic neuritis and other demyelinating disorders have been associated with the use of some of these agents.2 When this class of medications was tested on people who already had MS, there was an increase in disease activity.3

Autoimmune Disease and Treatment
Medications called tumor necrosis factor antagonists or anti-tumor necrosis factor agents, such as Enbrel(r) (etanercept), Remicade(r) (infliximab), and a Humira(r) (adalimubab), are used in the treatment of rheumatoid arthritis and other autoimmune diseases, including psoriatic arthritis and Crohn's disease.

Drugs that inhibit TNF decrease the inflammation in these diseases and have been shown to halt the progression of joint destruction and reduce the signs and symptoms of both rheumatoid and psoriatic arthritis. Enbrel(r) is now recommended as an initial therapy for rheumatoid arthritis. It appears, however, that drugs that inhibit TNF may also have a negative impact on the immune system. Some patients have developed serious infections, such as tuberculosis, while taking Enbrel(r).

Tumor necrosis factor and MS
Although TNF seems to be involved in the inflammation seen in other autoimmune diseases, its precise role in MS is controversial. When TNF was blocked in EAE, an animal model of MS, severity of EAE was decreased. In humans, MS plaques and cerebrospinal fluid have been shown to contain high levels of TNF. However, anti-tumor necrosis factor medications have been associated with an increase in exacerbations and a worsening of symptoms in people who have MS.4 This may be because TNF alpha antagonists cannot cross the blood brain barrier and work on the cells in the central nervous system that are affected in MS, whereas in rheumatoid arthritis and Crohn's disease, they can go to work directly on the diseased cells in the joints and in the bowel. Another explanation is that when TNF alpha antagonists exert their effect outside the central nervous system, they heighten the activity of a type of T cell involved in the autoimmune response, precipitating further MS symptoms.

Although the causal relationship between TNF alpha antagonists and either the onset or worsening of MS remains unclear, the National MS Society advises against the use of TNF alpha antagonists in people with MS. Patients who develop new neurological symptoms while on any TNF alpha antagonist medication should be seen by a neurologist and monitored with frequent MRIs.5

1 Mohan, N., et al. "Demyelination Occurring During Anti-Tumor Necrosis Factor Alpha Therapy for Inflammatory Arthritides." Arthritis and Rheumatism; 44: no.12 (December 2001) 2862.
2 Immunex Corporation. "Enbrel(r) package insert." Seattle, Washington: 2002.
3 Robinson, W.H., Genovese, M.C., and Moreland, L.W. Demyelinating and Neurologic Events Reported in Association With Tumor Necrosis Factor Alpha Antagonism. Arthritis and Rheumatism; 44: no. 9 (September, 2001) 1978.
4 Robinson, W.H. "Demyelinating and Neurologic Events..." 1978.
5 Mohan, N. et al. "Demyelination Occurring During Anti-Tumor Necrosis Factor Therapy...) 2868.

Nutritional biomarkers in Alzheimer's disease: the association between carotenoids, n-3 fatty acids, and dementia severity.
... Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty acids, such as n-3 fatty acids from oxidation, and are potentially important for Alzheimer's disease (AD) prevention and treatment... Moderately severe AD patients (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and beta-carotene, compared to mild AD patients (MMSE=24-27) or controls...
http://www.ncbi.nlm.nih.gov/pubmed/18334754

Plasma carotenoid levels and cognitive performance in an elderly population: results of the EVA Study
... METHODS: We examined, in a cross-sectional analysis, the relationship between cognitive performance (assessed by the Mini-Mental State Examination, Trail Making Test Part B, Digit Symbol Substitution, Finger Tapping Test, and Word Fluency Test) and different plasma carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and trans-beta-carotene and cis-beta-carotene) in a healthy elderly population (the EVA,"Etude du Vieillissement Artériel," study; n = 589, age = 73.5 +/- 3 years).

RESULTS:

Logistic regression showed that participants with the lowest cognitive functioning (<25th percentile) had a higher probability of having low levels of specific plasma carotenoids (<1st quartile): lycopene and zeaxanthin.

... CONCLUSION: Even if it is not possible to affirm if these low levels of carotenoids precede or are the consequence of cognitive impairment, our results suggest that low carotenoid levels could play a role in cognitive impairment. The biological significance of our findings needs further research.
http://www.ncbi.nlm.nih.gov/pubmed/17389729

Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration.
J Neurosci Res. 2010 Jul;88(9):1970-84.
Wang L, Ankati H, Akubathini SK, Balderamos M, Storey CA, Patel AV, Price V, Kretzschmar D, Biehl ER, D'Mello SR.

Department of Molecular and Cell Biology, University of Texas at Dallas, Richardson, TX, USA.
Abstract

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease and conditions such as ischemic stroke affect millions of individuals annually and exert an enormous financial burden on society. A hallmark of these conditions is the abnormal loss of neurons. Currently, there are no effective strategies to prevent neuronal death in these pathologies. We report that several 2-arylidine and 2-hetarylidin derivatives of the 1,4-benzoxazines class of compounds are highly protective in tissue culture models of neurodegeneration. Results obtained using pharmcalogical inhibitors indicate that neuroprotection by these compounds does not involve the Raf-MEK-ERK or PI-3 kinase-Akt signaling pathways nor other survival-promoting molecules such as protein kinase A (PKA), calcium calmodulin kinase A (CaMK), and histone deacetylases (HDACs). We tested one of these compounds, (Z)-6-amino-2-(3',5'-dibromo-4'-hydroxybenzylidene)-2H-benzo[b][1,4]oxazin-3(4H)-one, designated as HSB-13, in the 3-nitropropionic acid (3-NP)-induced mouse model of Huntington's disease. HSB-13 reduced striatal degeneration and improved behavioral performance in mice administered with 3-NP. Furthermore, HSB-13 was protective in a Drosophila model of amyloid precursor protein (APP) toxicity. To understand how HSB-13 and other 1,4-benzoxazines protect neurons, we performed kinase profiling analyses. These analyses showed that HSB-13 inhibits GSK3, p38 MAPK, and cyclin-dependent kinases (CDKs). In comparison, another compound, called ASK-2a, that protects cerebellar granule neurons against low-potassium-induced death inhibits GSK3 and p38 MAPK but not CDKs. Despite its structural similarity to HSB-13, however, ASK-2a is incapable of protecting cortical neurons and HT22 cells against homocysteic acid (HCA)-induced or Abeta toxicity, suggesting that protection against HCA and Abeta depends on CDK inhibition. Compounds described in this study represent a novel therapeutic tool in the treatment of neurodegenerative diseases.

PMID: 20143421 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/20143421


Novel Compounds Show Early Promise in Treatment of Parkinson's, Huntington's, Alzheimer's

ScienceDaily (Dec. 7, 2010) — Investigators at Southern Methodist University and The University of Texas at Dallas have discovered a family of small molecules that shows promise in protecting brain cells against nerve-degenerative diseases such as Parkinson's, Alzheimer's and Huntington's, which afflict millions...
http://www.sciencedaily.com/releases/2010/12/101207131737.htm

New Compound Could Protect Brain Cells, Fight Neurodegenerative Diseases
December 8, 2010 10:09 AM
Tiffany Kaiser
"Additional research needs to be done, but these compounds have the potential for stopping or slowing the relentless loss of brain cells in diseases such as Alzheimer's and Parkinson's," said D'Mello. "The protective effect that they display in tissue culture and animal models of neurodegenerative disease provides strong evidence of their promise as drugs to treat neurodegenerative disorders."
http://www.dailytech.com/New+Compound+Could+Protect+Brain+Cells+Fight+Neurodegenerative+Diseases/article20345c.htm

Novel 2-Alkylamino-1,4-benzoxazine Derivatives as Potent Neuroprotective
Agents: Structure-Activity Relationship Studies
J. Med. Chem. 2005, 48, 1282-1286

Estelle Blattes,† Brian Lockhart,‡ Pierre Lestage,‡ Leslie Schwendimann,§ Pierre Gressens,§ Maurice-Bernard Fleury,† and Martine Largeron†,*

UMR 8638 CNRS - Universite´ Rene´ Descartes, Synthe`se et Structure de Mole´cules d’Inte´reˆt Pharmacologique, Faculte´ des Sciences Pharmaceutiques et Biologiques, 4 Avenue de l’Observatoire, 75270 Paris Cedex 06, France, Institut de Recherches Servier, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, France, and INSERM U 676 and Service de Neurologie Pe´diatrique, Hoˆpital Robert Debre´, 48 boulevard Se´rurier, 75019 Paris, France
Received August 25, 2004

2-Alkylamino-substituted-1,4-benzoxazine derivatives, a new class of potential neuroprotective agents, were synthesized and examined for their intrinsic cytotoxicity and their capacity to inhibit oxidative stress-mediated neuronal degeneration in vitro. Through structure-activity relationship studies, the 3,3-diphenyl-substituted-1,4-benzoxazine derivative 3l was identified as the optimal candidate, owing to its potent neuroprotective activity, without the manifestation of intrinsic cytotoxicity. Accordingly, 3l proved to be effective in an animal model of excitotoxic lesions in newborn mice...Oxygen, though essential for aerobic metabolism, can be converted to toxic metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals, collectively known as reactive oxygen species (ROS). When ROS generation exceeds the capacity of endogenous enzymatic and nonenzymatic antioxidant defense systems, tissues become vulnerable to damage, as the result of a widely accepted phenomenon called oxidative stress.1... Consequently, supplementation with exogenous antioxidants could represent an important therapeutic potential to minimize central nervous system damage.4 Hence, there is considerable interest in the discovery and development of efficient synthetic antioxidants. In the course of our search for new neuroprotective agents, we have previously reported the synthesis of novel 8-alkylamino-substituted-1,4-benzoxazine derivatives 1, as well as 3-alkylamino-2,4-dihydroxybenzophenones 2 (Chart 1). From their capacity to inhibit oxidative stress-mediated neuronal degeneration in vitro, these compounds were found to be potent neuroprotective agents, with activity close to that of standard R-tocopherol [a form of vitamin E].5 From the combined results of both intrinsic cytotoxicity and neuroprotection, substituted 1,4-benzoxazines were identified as the best candidates for therapeutic potential.
http://www.u676.org/Documents/Blattes-JMedChem-05.pdf
http://www.ncbi.nlm.nih.gov/pubmed/15715499

Identification of 1,4-Benzoxazin-3-ones in Maize Extracts by Gas-Liquid Chromatography and Mass Spectrometry
Plant Physiol. (1979) 63, 9-13

ABSTRACT
Gas-liquid chromatography-mass spectrometry (GLC-MS) has been used for the separation, detection, and identification of 1,4-benzoxazin-3-ones (hydroxamic acids and lactams) and benzoxazolinones found in maize (Zea mays L.) extracts. Compounds of interest were partitioned into ethyl acetate from aqueous maize seedling extracts. For analysis by GLC-MS, trimethylsilyl derivatives were prepared, chromatographed on a column of 3% OV-1, and detected in the mass spectrometer. Mass spectra were obtained for all peaks present in extracts of four maize lnes. A data comparison system was developed for relating unidentified spectra to the spectra of the reference compounds. Based on spectral comparisons, three hydroxamic acids (2,4-dihydroxy-2H-1, 4-benzoxazin-3(4H)-one; 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one; and 2,4-dihydroxy-7,8-dimethoxy-2H-1,4-benzoxazin-3(4H)-one), three lactams (2-hydroxy-2H-1,4-benzoxazin-3(4H)-one; 2,7-ihydroxy-2H-I,4-benzoxazin-3(4H)-one; and 2-hydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one), one benzoxazolinone (6-methoxybenzoxazolinone), and two organic acids (malic and aconitic) were identified in the extracts. In addition, one other hydroxamic acid and one other related compound were tentatively identified based on mass spectral evidence.
http://www.plantphysiol.org/cgi/reprint/63/1/9.pdf
http://www.ncbi.nlm.nih.gov/pubmed/16660700

Could lysine supplementation prevent Alzheimer’s dementia? A novel hypothesis
Neuropsychiatr Dis Treat. 2010 Oct 27;6:707-10.

Rubey RN.

Retired, Red Lodge, Montana, USA.
Abstract

There is a growing body of evidence that implicates the herpes simplex type 1 virus (HSV-1) in the development of Alzheimer's dementia (AD). HSV-1 has been found to be present in the cerebrum of the great majority of older adults, and in many of the same areas of the brain that are affected by AD. When active, the virus may contribute to the formation of the neuro-fibrillary tangles and amyloid plaques characteristic of AD. Like AD, HSV-1 encephalitis may cause long term memory loss. HSV-1 replication is suppressed in lysine-rich/arginine - poor environments, and population studies suggest that diets high in lysine and low in arginine may be associated with lower rates of AD. There are no prospective studies of the efficacy of lysine supplementation to prevent or reduce the incidence of AD. Supplementation with adequate doses of lysine could prevent the development of AD.

PMID: 21127688 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21127688
Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987503/?tool=pubmed
           http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987503/pdf/ndt-6-707.pdf

The postsynaptic density (PSD) is a cytoskeleton specialization at neuronal synapses that was originally identified as an electron-dense region at the membrane of a postsynaptic neuron, as viewed by electron microscopy. PSDs are usually composed of L-glutamate neurotransmitter receptors, their molecular scaffolding molecules, cell adhesion molecules and a diverse set of other signaling proteins. PSDs vary in size and composition among brain regions. Many of the PSD proteins contain PDZ domains...
http://en.wikipedia.org/wiki/Postsynaptic_density

Scientists find gene clue to 130 brain diseases
Dec 19, 2010

"We found over 130 brain diseases involve the PSD -- far more than expected," said Grant. "The human PSD is at centre stage of a large range of human diseases affecting millions of people."... It also shows that the synapses in rodents are more similar to humans than previously thought, suggesting that mice and rats are good models for examining human brain disease, he said...
http://www.breitbart.com/article.php?id=CNG.e3e5f80d414a6156c689824808235ca9.261&show_article=1

Hope for millions as brain study unlocks secrets of Alzheimer's
By Steve Connor, Science Editor
Monday, 20 December 2010
... "Our findings have shown that the human post-synaptic density is at centre stage of a large range of human diseases affecting many millions of people," Professor Grant said. "We found over 130 brain diseases involved the post-synaptic density – far more than expected...
http://www.independent.co.uk/news/science/hope-for-millions-as-brain-study-unlocks-secrets-of-alzheimers-2164844.html


Genetic Basis of Brain Diseases: Set of Proteins Account for Over 130 Brain Diseases

ScienceDaily (Dec. 20, 2010) — Scientists have isolated a set of proteins that accounts for over 130 brain diseases, including diseases such as Alzheimer's disease, Parkinson's disease, epilepsies and forms of autism and learning disability...
http://www.sciencedaily.com/releases/2010/12/101219140817.htm

Journal Reference:

   1. Àlex Bayés, Louie N van de Lagemaat, Mark O Collins, Mike D R Croning, Ian R Whittle, Jyoti S Choudhary, Seth G N Grant. Characterisation of the proteome, diseases and evolution of the human postsynaptic density. Nature Neuroscience, December 19, 2010 DOI: 10.1038/nn.2719
http://dx.doi.org/10.1038/nn.2719

Characterization of the proteome, diseases and evolution of the human postsynaptic density
Àlex Bayés, Louie N van de Lagemaat, Mark O Collins, Mike D R Croning, Ian R Whittle, Jyoti S Choudhary & Seth G N Grant

Nature Neuroscience (2010) doi:10.1038/nn.2719 23 June 2010
Accepted 12 November 2010 Published online 19 December 2010

We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins. hPSD mutations cause 133 neurological and psychiatric diseases and were enriched in cognitive, affective and motor phenotypes underpinned by sets of genes. Strong protein sequence conservation in mammalian lineages, particularly in hub proteins, indicates conserved function and organization in primate and rodent models. The hPSD is an important structure for nervous system disease and behavior...
http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.2719.html

Rosemary: Aricept's Little Sister?
"Rosemary contains more than a dozen antioxidants and a half-dozen compounds reported to prevent the breakdown of acetylcholine. It's fabulous that the classical herb of remembrance has so many compounds that might help people suffering from Alzheimer’s."...
http://alzheimersweekly.com/content/rosemary-aricepts-little-sister


Rosemary fights aging, stroke and dementia
Published: Oct. 31, 2007
LA JOLLA, Calif., Oct. 31 (UPI) -- Rosemary chicken -- at least the rosemary -- may be one answer to preventing dementia and the effects of aging, says a team of U.S. and Japanese researchers.

Researchers led by Dr. Stuart Lipton of Burnham Institute in La Jolla, Calif., and Dr. Takumi Satoh of Iwate University in Japan say the herb rosemary contains an ingredient that fights off free radical damage in the brain...
http://www.upi.com/Health_News/2007/10/31/Rosemary-fights-aging-stroke-and-dementia/UPI-58061193860405/

http://www.sciencedaily.com/releases/2010/11/101129101914.htm

Bryostatins are a group of macrolide lactones first isolated in the 1960s by George Pettit from extracts of a species of bryozoan, Bugula neritina. The structure of bryostatin 1 was determined in 1982.[1] Until today 20 different bryostatins have been isolated.[2] Bryostatins are a potent modulators of protein kinase C. They are currently under investigation as anti-cancer agents and as a memory enhancing agent...

FDA Gives Clinical Trial Green Light On Drug To Treat Alzheimer’s Disease

Previous Studies Show Bryostatin Protects Against Alzheimer’s Protein, Rewires and Repairs Brain Damage

Morgantown, WV (April 22, 2009) - The Food and Drug Administration (FDA) has given the Blanchette Rockefeller Neurosciences Institute (BRNI) the go-ahead to conduct Phase II clinical trials of Bryostatin for the treatment of Alzheimer’s disease patients. The drug showed pre-clinical efficacy to not only treat Alzheimer’s disease symptoms, but also its underlying causes.

“We are very excited about the FDA’s agreement for BRNI to move forward with clinical trials,” said Dr. Daniel Alkon, Scientific Director of BRNI. “Bryostatin shows the promise to repair and protect against neurodegeneration caused by Alzheimer’s disease, stroke and other brain trauma, as well as enhance the brain’s normal memory functions.”

Bryostatin was originally created as an anti-cancer chemotherapy. When BRNI scientists extensively tested PKC activators against Alzheimer’s disease models, they discovered the drug’s hidden potential to stop Alzheimer’s disease.Over the past six years, the drug has shown remarkable possibilities. In preclinical testing, BRNI scientists experimented with Bryostatin on three species of Alzheimer’s disease transgenic mice, each species based on different human Alzheimer’s disease genes. The test results revealed that Bryostatin, and a related class of drugs discovered at BRNI, can reduce the toxic Alzheimer’s disease protein A Beta, restore lost synapses, and protect against the loss of memory functions. Bryostatin has been shown to enhance and restore memory by rewiring connections in the brain previously destroyed by stroke, head trauma, or aging itself.

The Phase II trials, slated to begin in approximately two to four months, will test these preclinical findings on human Alzheimer’s disease patients as well as controls, along with Bryostation’s effects on molecular targets in the human body, such as the signaling enzyme PKC. The drug’s side effects will also be carefully monitored using low doses that were previously found to be generally benign in human cancer patients.

Clinical trials for Alzheimer's drug at BRNI

Chestnut Ridge Center, West Virginia University’s psychiatric hospital, will conduct the trials on Bryostatin, a drug originally created as an anti-cancer chemotherapy...
http://backup.wvpubcast.org/newsarticle.aspx?id=10302


Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics Study of Bryostatin 1 in Patients With Alzheimer's Disease
http://clinicaltrial.gov/ct2/show/NCT00606164

The Blanchette Rockefeller Neurosciences Institute Identifies Groundbreaking New Therapies for Prevention and Treatment of Alzheimer's Disease

MORGANTOWN, W.Va., Jan. 11, 2011 /PRNewswire-USNewswire/ -- A Blanchette Rockefeller Neurosciences Institute (BRNI) study published today in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer's Disease and identifies promising pharmaceutical solutions for the devastating condition... Alzheimer's Disease is not primarily a disease of plaques and tangles as many had previously concluded, it is most importantly a disease of synapses," said Dr. Daniel Alkon, the scientific director of BRNI and co-author of the study, "This study found that treatments that target the loss of synapses in the Alzheimer's brain, can virtually eliminate all other elements of the disease – elevation of the toxic protein, A Beta, the loss of neurons, the appearance of plaques, and loss of cognitive function; the animals' brains were normalized."...
http://www.prnewswire.com/news-releases/the-blanchette-rockefeller-neurosciences-institute-identifies-groundbreaking-new-therapies-for-prevention-and-treatment-of-alzheimers-disease-113303809.html



Morgantown, WV, January 12, 2011 – A Blanchette Rockefeller Neurosciences Institute (BRNI) study published today in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer’s Disease and identifies promising pharmaceutical solutions for the devastating condition that affects more than 5 million people in the United States.  The BRNI study is the first to achieve fundamental molecular understanding of how synapses are lost in Alzheimer’s Disease before the plaques and tangles develop.  At the same time, it is the first study to demonstrate the comprehensive benefits of synaptogenic compounds in treating Alzheimer’s Disease...
http://www.brni.org/news/articles/The_Blanchette_Rockefeller_Neurosciences_Institute_Identifies_Gr,46.aspx


PKC {varepsilon} Activation Prevents Synaptic Loss, A{beta} Elevation, and Cognitive Deficits in Alzheimer's Disease Transgenic Mice.
J Neurosci. 2011 Jan 12;31(2):630-43.
Hongpaisan J, Sun MK, Alkon DL.

Blanchette Rockefeller Neurosciences Institute at West Virginia University, Morgantown, West Virginia 26505, and Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Abstract

Among the pathologic hallmarks of Alzheimer's disease (AD) neurodegeneration, only synaptic loss in the brains of AD patients closely correlates with the degree of dementia in vivo. Here, we describe a molecular basis for this AD loss of synapses: pathological reduction of synaptogenic PKC isozymes and their downstream synaptogenic substrates, such as brain-derived neurotrophic factor. This reduction, particularly of PKC α and ε, occurs in association with elevation of soluble β amyloid protein (Aβ), but before the appearance of the amyloid plaques or neuronal loss in the Tg2576 AD transgenic mouse strain. Conversely, treatment of the Tg2576 mouse brain with the PKC activator, bryostatin-1, restores normal or supranormal levels of PKC α and ε, reduces the level of soluble Aβ, prevents and/or reverses the loss of hippocampal synapses, and prevents the memory impairment observed at 5 months postpartum. Similarly, the PKC ε-specific activator, DCP-LA, effectively prevents synaptic loss, amyloid plaques, and cognitive deficits (also prevented by bryostatin-1) in the much more rapidly progressing 5XFAD transgenic strain. These results suggest that synaptic loss and the resulting cognitive deficits depend on the balance between the lowering effects of Aβ on PKC α and ε versus the lowering effects of PKC on Aβ in AD transgenic mice.

PMID: 21228172 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/21228172


New Therapies for Prevention and Treatment of Alzheimer's Disease Identified

ScienceDaily (Jan. 14, 2011) — A Blanchette Rockefeller Neurosciences Institute (BRNI) study published in the Journal of Neuroscience reveals underlying causes for the degeneration of synapses in Alzheimer's Disease and identifies promising pharmaceutical solutions for the devastating condition that affects more than 5 million people in the United States...
http://www.sciencedaily.com/releases/2011/01/110112110739.htm

Wikipedia:

Transcranial magnetic stimulation (TMS) is a noninvasive method to cause depolarization in the neurons of the brain. TMS uses electromagnetic induction to induce weak electric currents using a rapidly changing magnetic field; this can cause activity in specific or general parts of the brain with minimal discomfort, allowing the functioning and interconnections of the brain to be studied. A variant of TMS, repetitive transcranial magnetic stimulation (rTMS), has been tested as a treatment tool for various neurological and psychiatric disorders including migraines, strokes, Parkinson's disease, dystonia, tinnitus, depression and auditory hallucinations...
http://en.wikipedia.org/wiki/Transcranial_magnetic_stimulation

Study on the Effect of External Magnetic Stimulation on Patients With Parkinson's Disease
The purpose of this research study is to test the usefulness of external magnetic stimulation (EMS) for treating the motor, cognitive, and neuropsychiatric symptoms of Parkinson's disease (PD).

Participants with Parkinson's disease will be recruited at the PADRECC of the Philadelphia VA Medical Center. Enrolled participants will be randomly assigned to receive either active external magnetic stimulation or fake stimulation. The external magnetic stimulation is delivered by wearing a helmet that is embedded with many small circuits which produce a very small magnetic field around the head. The helmet is to be worn daily for two minutes immediately before bedtime for three months in a row. The helmet is for investigational use only and has not been approved for use by the FDA.
http://clinicaltrials.gov/ct2/show/NCT00841464

Brain Stimulation Technique Boosts Language Ability in Alzheimer's Patients

ScienceDaily (June 25, 2010) — A brain stimulation technique, known as repetitive transcranial magnetic stimulation, boosts the language ability of patients with Alzheimer's disease, suggests preliminary research, published online in the Journal of Neurology, Neurosurgery and Psychiatry...
http://www.sciencedaily.com/releases/2010/06/100623212633.htm

Learn More Quickly by Transcranial Magnetic Brain Stimulation, Study in Rats Suggests

ScienceDaily (Jan. 29, 2011)

...Transcranial magnetic stimulation (TMS) is a relatively new method of pain-free stimulation of cerebral nerve cells. The method, which was presented by Anthony Barker for the first time in 1985, is based on the fact that the cortex, the rind of the brain located directly underneath the skull bone, can be stimulated by means of a magnetic field... "In general, the activity of the cells drops as a result of a low-frequency stimulation, i.e. with one magnetic pulse per second. At higher frequencies from five to 50 pulses per second, the activity of the cells increases. This rhythm is based on the natural theta rhythm of four to seven Hertz which can be observed in an EEG,"...
http://www.sciencedaily.com/releases/2011/01/110128121629.htm

More Evidence That Alzheimer's Disease May Be Inherited from Your Mother

ScienceDaily (Feb. 28, 2011) — Results from a new study contribute to growing evidence that if one of your parents has Alzheimer's disease, the chances of inheriting it from your mother are higher than from your father. The study is published in the March 1, 2011, print issue of Neurology®, the medical journal of the American Academy of Neurology... The researchers found that people with a mother who had Alzheimer's disease had twice as much gray matter shrinkage as the groups who had a father or no parent with Alzheimer's disease. In addition, those who had a mother with Alzheimer's disease had about one and a half times more whole brain shrinkage per year compared to those who had a father with the disease. Shrinking of the brain, or brain atrophy, occurs in Alzheimer's disease...
http://www.sciencedaily.com/releases/2011/02/110228163026.htm

Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease.
Neurology. 2011 Mar 1;76(9):822-9.
Honea RA, Swerdlow RH, Vidoni ED, Burns JM.

Department of Neurology, University of Kansas School of Medicine, 2100 West 36th Ave., Suite 110, Kansas City, KS 66160 rhonea@kumc.edu.
Abstract

OBJECTIVE: Beyond age, having a family history is the most significant risk factor for Alzheimer disease (AD). This longitudinal brain imaging study examines whether there are differential patterns of regional gray matter atrophy in cognitively healthy elderly subjects with (FH+) and without (FH-) a family history of late-onset AD.

METHODS: As part of the KU Brain Aging Project, cognitively intact individuals with a maternal history (FHm, n = 11), paternal history (FHp, n = 10), or no parental history of AD (FH-, n = 32) similar in age, gender, education, and Mini-Mental State Examination (MMSE) score received MRI at baseline and 2-year follow-up. A custom voxel-based morphometry processing stream was used to examine regional differences in atrophy between FH groups, controlling for age, gender, and APOE ε4 (APOE4) status. We also analyzed APOE4-related atrophy.

RESULTS: Cognitively normal FH+ individuals had significantly increased whole-brain gray matter atrophy and CSF expansion compared to FH-. When FH+ groups were split, only FHm was associated with longitudinal measures of brain change. Moreover, our voxel-based analysis revealed that FHm subjects had significantly greater atrophy in the precuneus and parahippocampus/hippocampus regions compared to FH- and FHp subjects, independent of APOE4 status, gender, and age. Individuals with an ε4 allele had more regional atrophy in the frontal cortex compared to ε4 noncarriers.

CONCLUSIONS: We conclude that FHm individuals without dementia have progressive gray matter volume reductions in select AD-vulnerable brain regions, specifically the precuneus and parahippocampal gyrus. These data complement and extend reports of regional cerebral metabolic differences and increases in amyloid-β burden in FHm subjects, which may be related to a higher risk for developing AD.

PMID: 21357834 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21357834

If your mother has Alzheimer's, you are at greater risk: Study
By Karen Kaplan, Los Angeles Times March 1, 2011
http://www.canada.com/health/Study+your+mother+Alzheimer+greater+risk/4361784/story.html

Liver, Not Brain, May Be Origin of Alzheimer’s Plaques

ScienceDaily (Mar. 3, 2011) — Unexpected results from a Scripps Research Institute and ModGene, LLC study could completely alter scientists' ideas about Alzheimer's disease -- pointing to the liver instead of the brain as the source of the "amyloid" that deposits as brain plaques associated with this devastating condition. The findings could offer a relatively simple approach for Alzheimer's prevention and treatment... The mice were injected with Gleevec twice a day for seven days; then plasma and brain tissue were collected, and the amount of beta amyloid in the blood and brain was measured. The findings: the drug dramatically reduced beta amyloid not only in the blood, but also in the brain where the drug cannot penetrate. Thus, an appreciable portion of brain amyloid must originate outside of the brain, and imatinib represents a candidate for preventing and treating Alzheimer's...
http://www.sciencedaily.com/releases/2011/03/110303134435.htm

J. Gregor Sutcliffe, Peter B. Hedlund, Elizabeth A. Thomas, Floyd E. Bloom, Brian S. Hilbush. Peripheral reduction of β-amyloid is sufficient to reduce brain β-amyloid: Implications for Alzheimer's disease. Journal of Neuroscience Research, March 3, 2011 DOI: 10.1002/jnr.2260

Star Scientific Shares Spike As It Stumbles Onto A Potential Alzheimer's Cure
businessinsider.com
Mar. 11, 2011, 2:37 PM 
CIGrX
Star Scientific, a manufacturer of smokeless tobacco products... isolated a compound in nicotine called antabine [sic] which reduces the protein amyloid. Amyloid is what many scientists believe to be the main cause of Alzheimer's... reduces inflammation in inflamed human brain tissue... by about 100%...
http://www.businessinsider.com/star-scientific-alzheimers-cure-2011-3

Analytical Determination of Nicotine and Related Compounds and their Metabolites
by J.W. Gorrod and P. Jacob III
(Nov 16, 1999)
Ch. 4, pg. 72
http://books.google.com/books?id=-gyynUUv2sAC&lpg=PA69&ots=2HEUs7nRSc&dq=%22S-(-)anatabine%22%20nicotiana&lr&pg=PA69#v=onepage&q&f=false

CIGX - a Therapy for the Scourge of Alzheimer's
By Dr. John L Faessel
October 08, 2010

“Preliminary tests performed by the Roskamp Institute show that when the compound developed by Rock Creek (the Star subsidiary) is applied to cells, B-amyloid is reduced. Also, the compound appears to encourage new neuronal cell growth.”... It should be noted that CigRx™ is a Tic-Tac type lozenge that temporarily reduces the urge to smoke; it is a non-prescription, over-the-counter, and a non-nicotine nutraceutical... Anatabine is found in tobacco as well as in peppers, eggplant and green tomatoes. Fresh Nicotiana tabacum, the plant variety most commonly used for the production of cigarette tobacco, contains 3.9% anatabine. (Source: Merck Index)...
http://www.benzinga.com/trading-ideas/long-ideas/10/10/516006/cigx-a-therapy-for-the-scourge-of-alzheimers

Is tobacco the unlikely Alzheimer's cure?
Star Scientific is developing CigRx, a nicotene-based compound that could help reduce brain inflamation and fight the disease
By InvestorPlace on Tue, Mar 1, 2011 10:27 AM
By Jeff Reeves, Editor, InvestorPlace.com
...So why haven’t you heard of this development? Well, because the results are preliminary and Star Scientific is burying its study on the potential cure in legalese and confusing press releases...
http://money.msn.com/top-stocks/post.aspx?post=43270d83-c6f9-43f2-bf2a-708275011028

Star Scientific: Astonishing Research With Unfathomable Market Potential
Seeking Alpha June 7, 2011
...Mullan played videos showing once-Alzheimer’s-afflicted mice beginning not only to remember again, but becoming able to add critical new information to the cognitive equation and, thus, to change behavior so as even to improve their lot. That’s impossible for a “demented” mouse...
http://seekingalpha.com/article/273675-star-scientific-astonishing-research-with-unfathomable-market-potential?source=yahoo

Anatabine lowers Alzheimer's Aβ production in vitro and in vivo.
Eur J Pharmacol. 2011 Nov 30;670(2-3):384-91. Epub 2011 Sep 19.
Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.
Source: Roskamp Institute, 2040 Whitfield Avenue, Sarasota, FL 34243, USA. dparis@rfdn.org

Abstract:
Brain Aβ accumulation represents a key pathological hallmark in Alzheimer's disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aβ production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer's disease. In vitro, anatabine lowers Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a dose dependent manner and reduces sAPPβ production without impacting sAPPα levels suggesting that anatabine lowers Aβ production by mainly impacting the β-cleavage of APP. Additionally, we show that anatabine lowers NFκB activation at doses that inhibit Aβ production in vitro. Since NFκB is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aβ production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aβ lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a transgenic mouse model of Alzheimer's disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aβ accumulation.
PMID: 21958873 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/21958873
http://www.sciencedirect.com/science/article/pii/S0014299911009836

Peer Reviewed Anatabine Study a Game Changer for Star Scientific
Oct 6, 2011
…We observed that at a dose of 2 mg/kg, anatabine significantly lowers plasma CRP levels confirming that at this dosage anatabine displays an anti-inflammatory activity in vivo. [ 1 kg = 2.2lb, so 220lbs is about 100kg, meaning someone weighing 220lbs would have to take 200mg?]
http://seekingalpha.com/instablog/576542-dr-john-faessel/224129-peer-reviewed-anatabine-study-a-game-changer-for-star-scientific

Roskamp Institute in Sarasota, Florida, have shown that an anatabine compound supplied by Rock Creek has beneficial effects on memory and learning in animal models of Alzheimer’s Disease. Michael Mullan, MD, Ph.D., CEO of the Roskamp Institute and his colleague, Dr. Daniel Paris, published these findings in October, 2011 in the European Journal of Pharmacology
http://www.mullanalzheimer.com/category/dementia/

Pharmacologic Blockade of 5-Lipoxygenase Improves the Amyloidotic Phenotype of an Alzheimer's Disease Transgenic Mouse Model: Involvement of γ-Secretase.
Jin Chua and Domenico Pratic.
The American Journal of Pathology, Volume 178, Issue 4, April 2011, Pages 1762-1769
Abstract

The 5-lipoxygenase (5-LO) enzyme is widely distributed within the central nervous system. Previous works showed that this protein is up-regulated in Alzheimer's disease (AD) and that its genetic absence results in a reduction of amyloid β (Aβ) levels in Tg2576 mice. In the present study, we examined the effect of 5-LO pharmacological inhibition on the amyloidotic phenotype of these mice. Aβ deposition in the brains of mice receiving zileuton, a selective and specific 5-LO inhibitor, was significantly reduced when compared with control Tg2576 mice receiving vehicle. This reduction was associated with a similar decrease in brain Aβ peptides levels. Zileuton treatment did not induce any change in the steady state levels of amyloid-β precursor protein (APP), BACE1 or ADAM10. By contrast, it resulted in a significant reduction of presenilin 1 (PSEN1, alias PS1), nicastrin (NCSTN) , presenilin enhancer 2 homolog (PSNEN, alias, Pen-2), and anterior pharynx defective 1 (APH-1), the four components of the γ-secretase complex-at the protein and message level. Furthermore, in vitro studies confirmed that zileuton prevents Aβ formation by modulating γ-secretase complex levels without affecting Notch signaling. These data establish a functional role for 5-LO in the pathogenesis of AD-like amyloidosis, whereby it modulates the γ-secretase pathway. They suggest that pharmacological inhibition of 5-LO could provide a novel therapeutic opportunity for AD.
PMID:21435457
http://www.ncbi.nlm.nih.gov/pubmed/21435457


5-lipoxygenase protein modulates amyloid beta formation linked to Alzheimer's disease
Published on November 18, 2010 at 1:36 AM
http://www.news-medical.net/news/20101118/5-lipoxygenase-protein-modulates-amyloid-beta-formation-linked-to-Alzheimers-disease.aspx


Asthma drug shows promise in treatment of Alzheimer's disease
by Yasser Ali - March 27, 2011
http://www.themedguru.com/20110327/newsfeature/asthma-drug-shows-promise-treatment-alzheimers-disease-86144166.html

Scientists Discover Possible Treatment For Alzheimer's Disease In Asthma Drug
by T Goodman
http://inventorspot.com/articles/scientists_discover_possible_treatment_alzheimers_disease_asthma

Asthma drug could help fight Alzheimer's disease
2011-03-26 12:00:00
http://www.sify.com/news/asthma-drug-could-help-fight-alzheimer-s-disease-news-international-ld0mahhhcea.html

Prana's PBT2 -- Directly Restores Neurons Critical to Cognition
PLoS ONE Publication on PBT2 Consolidates the Underlying Mechanisms for the Preclinical and Clinical Benefits of PBT2 in Alzheimer's Disease
Press Release Source: Prana Biotechnology On Monday March 21, 2011, 11:30 am EDT 
...It has previously been shown that PBT2 neutralises the toxicity of the Alzheimer's Abeta protein by preventing the formation of toxic aggregates or oligomers*. These new results further explain how PBT2 can achieve such rapid improvements in cognition: by liberating copper and zinc trapped in amyloid deposits and returning those essential metals to neurons, where they are needed for normal function...
http://finance.yahoo.com/news/Pranas-PBT2-Directly-Restores-iw-2656906997.html?x=0


Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease.
Adlard PA, Bica L, White AR, Nurjono M, Filiz G, Crouch PJ, Donnelly PS, Cappai R, Finkelstein DI, Bush AI.
Oxidation Biology Laboratory, The Mental Health Research Institute, Parkville, Victoria, Australia.
PLoS One. 2011 Mar 11;6(3):e17669.

Abstract

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function.
PMID: 21412423 [PubMed] PMCID: PMC3055881
http://www.ncbi.nlm.nih.gov/pubmed/21412423
Free article: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017669

http://www.drugs.com/mmx/prazosin-hydrochloride.html

The noradrenergic system plays an important role in learning and memory. Moderate levels of norepinephrine released under control conditions strengthen prefrontal cortical functions via actions at post-synaptic α-2A adrenoceptors with high affinity for norepinephrine, while high levels of norepinephrine release during stress impair prefrontal cortex (PFC) cortical functions via α1 and possibly β1 receptors with lower affinity for norepinephrine. Thus, levels of norepinephrine determine whether prefrontal cortical or posterior cortical systems control behavior and thought. The successful use of atypical antipsychotics is thought to be related to their α1- and 5HT2A-blocking properties.

Aggressive behavior is associated with an increase in the number of α1-adrenoceptors in AD patients.

Two successful trials for treating AD agitation and aggression with Prazosin:

Two larger trials are now recruiting (as of October, 2010):

Changes in noradrenergic neurons appear to be similar in AD and Lewy body patients.

UCSF Study Links Inflammation in Brain to Some Memory Decline
Source: Jennifer O'Brien
University of California, San Francisco
April 13, 2011

High levels of a protein associated with chronic, low-grade inflammation in the brain correlate with aspects of memory decline in otherwise cognitively normal older adults, according to a study led by scientists at the University of California, San Francisco.

The study is being reported in a poster session at the American Academy of Neurology annual meeting on Wednesday, April 13, 2011.

Inflammation is part of the body’s natural immune response to tissue damage. However, chronic inflammation is associated with many diseases. In the brain, it is thought to play a role in aging and neurodegenerative diseases, such as Parkinson’s and Alzheimer’s. If further research determines that inflammation causes memory decline, anti-inflammatory drugs could prove useful in staving off the damage.

Studies in animals have shown that prolonged brain inflammation impairs function of the hippocampus, a region of the brain involved in storing and generating memory. It does so by disrupting the establishment of memories, a process known as long term potentiation.

The scientists in the study hypothesized that the presence of C-reactive protein (CRP), a marker of chronic low grade inflammation in the brain, would be associated with poorer memory creation and smaller medial-temporal lobes, which include the hippocampus...
http://www.ucsf.edu/news/2011/04/9712/ucsf-study-links-inflammation-brain-some-memory-decline


Study Links Inflammation in Brain to Some Memory Decline

ScienceDaily (Apr. 15, 2011)
http://www.sciencedaily.com/releases/2011/04/110413151645.htm

C-Reactive Protein
Definition

C-reactive protein is produced by the liver. The level of CRP rises when there is inflammation throughout the body.

This article discusses the blood test done to measures the amount of CRP in your blood...

...When second-generation antipsychotics (SGAs) were introduced, clinicians hoped the drugs would not have the potential to cause neuroleptic malignant syndrome (NMS)...

...NMS is believed to be caused by reduced dopamine activity in the brain  associated with dopamine antagonists, interruptions in nigrostriatal dopamine pathways, or withdrawal of dopaminergic  medications...

...NMS develops in an estimated 0.02% to 2.5% of patients treated with antipsychotics...

...case reports have made it clear that SGAs—like first-generation  antipsychotics (FGAs)—can precipitate this life-threatening neurologic emergency. ... 88 case reports indicate newer antipsychotics may cause atypical presentations (of NMS)...

Free article:
HTML: http://www.currentpsychiatry.com/article_pages.asp?AID=5258
PDF: http://www.currentpsychiatry.com/pdf/0608/0608CP_Article5.pdf

A Revolutionary Breakthrough in Alzheimer's Disease
(Nitrates and nitrites in foods may cause AD - Dr. Oz Show)
April 13, 2011

On April 7, 2011, a former surgeon general and Dr. Suzanne de la Monte appeared on the Dr. Oz Show entitled, "A Revolutionary Breakthrough in Alzheimer's Disease," (can be watched on his website) where she presented her important research. She is the doctor who coined the term "type 3 diabetes" in reference to Alzheimer's disease.She found by accident that giving a nitrosamine compound called streptozotocin, used to deliberately produce diabetes, caused Alzheimer's in her lab mice. She learned that the brain produces its own insulin. She further found that this compound causes production of toxic lipids in the liver that cross the blood brain barrier and damage certain cells such that the brain develops insulin deficiency and insulin resistance. Nitrites and nitrates, found in very many processed foods, are nitrosamine compounds and could very well explain the epidemics of Alzheimer's, autism, diabetes, MS, Parkinson's and ALS, along with other neurodegenerative diseases that have insulin resistance, decreased glucose uptake as part of the process. These diseases have all been on the increase as processed foods have taken over our diets. I will add Dr. de la Monte's references to the website http://www.coconutketones.com, in the very near future.

These nitrites and nitrates are in most bacon, ham and other meats, deli meats, whether pre-packaged or cut at the counter, processed cheeses, cereals, breads, pretzels, crackers, white flour and anything that contains white flour, certain beers, scotch and some other whiskeys. Something that has caught my attention for newborns and children: I found one of these offending compounds, thiamine mononitrate, in the Carnation infant formulas, some of the jarred baby foods, especially the junior combinations, cereals and other infant prepared foods such as macaroni and cheese...
http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/8724020397

Dietary vitamin E and selenium and toxicity of nitrite and nitrate

Toxicology. 2002 Nov 15;180(2):195-207.
Chow CK, Hong CB.
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY

Abstract

Nitrites and nitrates are important antimicrobial and flavoring/coloring agents in meat and fish products. However, nitrites and nitrates may cause methemoglobinemia and other illness, and may react with certain amines to form carcinogenic nitrosamines.

The nutritional status of vitamin E and selenium has long been associated with nitrite and nitrate toxicity, although the mechanism involved is not yet clear.

Information available recently shows that nitrites and nitrates are both oxidation products and ready sources of nitric oxide (NO√), that NO√ reacts rapidly with superoxide to form highly reactive peroxynitrite (ONOO−), and that vitamin E may mediate the generation and availability of superoxide and NO√.

Increased formation of ONOO− resulting from nitrite treatment and low intake of vitamin E and selenium may thus be the critical event leading to tissue damage and animal mortality observed previously.

The protection against the adverse effects of nitrites/nitrates by vitamin E is attributed to its ability to reduce ONOO− formation, while selenium exerts its protective effects via seleno-enzymes/compounds, which reduce ONOO− formed.

http://www.ncbi.nlm.nih.gov/pubmed/12324194

Evidence Lacking for Efficacy of Memantine in Treating Mild Alzheimer's Disease, Study Finds

ScienceDaily (Apr. 11, 2011) — An analysis of studies involving the drug memantine finds a lack of evidence for benefit when the drug is used to treat patients with mild Alzheimer disease, according to a report posted online that will appear in the August print issue of Archives of Neurology, one of the JAMA/Archives journals...
http://www.sciencedaily.com/releases/2011/04/110411163809.htm

Ferulic Acid: therapeutic potential through its antioxidant property.
J Clin Biochem Nutr. 2007 Mar;40(2):92-100.
Srinivasan M, Sudheer AR, Menon VP.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India.
Abstract

There has been considerable public and scientific interest in the use of phytochemicals derived from dietary components to combat human diseases. They are naturally occurring substances found in plants. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn and rice bran. It arises from metabolism of phenylalanine and tyrosine by Shikimate pathway in plants. It exhibits a wide range of therapeutic effects against various diseases like cancer, diabetes, cardiovascular and neurodegenerative. A wide spectrum of beneficial activity for human health has been advocated for this phenolic compound, at least in part, because of its strong antioxidant activity. FA, a phenolic compound is a strong membrane antioxidant and known to positively affect human health. FA is an effective scavenger of free radicals and it has been approved in certain countries as food additive to prevent lipid peroxidation. It effectively scavenges superoxide anion radical and inhibits the lipid peroxidation. It possesses antioxidant property by virtue of its phenolic hydroxyl group in its structure. The hydroxy and phenoxy groups of FA donate electrons to quench the free radicals. The phenolic radical in turn forms a quinone methide intermediate, which is excreted via the bile. The past few decades have been devoted to intense research on antioxidant property of FA. So, the present review deals with the mechanism of antioxidant property of FA and its possible role in therapeutic usage against various diseases.

PMID: 18188410 [PubMed]PMCID: PMC2127228
http://www.ncbi.nlm.nih.gov/pubmed/18188410
Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127228/
                http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127228/pdf/jcbn2007013.pdf


Ferulic Acid benefit as antioxidant supplement
by Ray Sahelian, M.D.
Ferulic acid is an antioxidant found naturally in plant cell walls, leaves and seeds. A good amount of ferulic acid is found in oats, brown rice, whole wheat, peanuts, apples, and pineapples... Ferulic acid is similar to curcumin in chemical structure. Ferulic acid is a derivative of trans-cinnamic acid and a precursor to vanillin... Coffee is particularly rich in bound phenolic acids, such as caffeic acid, ferulic acid...
http://www.raysahelian.com/ferulicacid.html


Inhibitory effects of long-term administration of ferulic acid on microglial activation induced by intracerebroventricular injection of beta-amyloid peptide (1-42) in mice.
Biol Pharm Bull. 2004 Jan;27(1):120-1.
Pharmaceutical Society of Japan
Vol. 27, No. 1
Kim HS, Cho JY, Kim DH, Yan JJ, Lee HK, Suh HW, Song DK.

Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon 200-702, Republic of Korea.
Abstract

Flavonoids and monophenolic compounds have been well described in recent years as antioxidants and scavengers of reactive oxygen and nitrogen species. In the present study, we aimed to characterize the effects of long-term administration of ferulic acid on the centrally administered beta-amyloid peptide (Abeta)(1-42)-induced activation of microglial cells in mice. Abeta(1-42) increased the immunoreactivity of OX-42, a microglial marker, and interferon-gamma in the hippocampus at 8 h after the intracerebroventricular injection. The effects were suppressed by long-term (4-week) pretreatment with ferulic acid. This inhibition of microglial cell activation may underlie the beneficial effects of long-term administration of ferulic acid on Abeta(1-42)-induced toxicity in vivo.

PMID: 14709913 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/14709913
Free PDF full text article: http://bpb.pharm.or.jp/bpb/200401/b01_0120.pdf


Protection against amyloid beta-peptide (1-42)-induced loss of phospholipid asymmetry in synaptosomal membranes by tricyclodecan-9-xanthogenate (D609) and ferulic acid ethyl ester: implications for Alzheimer's disease.
Biochim Biophys Acta. 2005 Jun 30;1741(1-2):140-8. Epub 2004 Dec 25.
Mohmmad Abdul H, Butterfield DA.

Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506, USA.
Abstract

Amyloid-beta (1-42) [Abeta (1-42)] deposition in the brain is a hallmark of Alzheimer's disease (AD) and has been shown to induce apoptosis and disrupt cellular ion homeostasis. Abeta (1-42) induces membrane lipid peroxidation, and 4-hydroxynonenal (HNE) and 2-propenal (acrolein) are the two reactive products of lipid peroxidation, which structurally modify proteins by covalent interaction and inhibit enzyme function. Phosphatidylserine (PS), an aminophospholipid, is sequestered in the inner leaflet of the plasma membrane in nonstimulated cells. An early signal of synaptosomal apoptosis is the loss of phospholipid asymmetry and the appearance of phosphatidylserine in the outer leaflet of the membrane. The ATP-requiring enzyme, flippase, maintains phospholipid asymmetry of PS. Here, we have investigated the inactivation of the transmembrane enzyme aminophospholipid-translocase (or flippase) by Abeta (1-42). Flippase activity depends on a critical cysteine residue, a putative site of covalent modification by the Abeta (1-42)-induced lipid peroxidation products, HNE or acrolein. The present study is aimed to investigate the protective effects of tricyclodecan-9-xanthogenate (D609) and ferulic acid ethyl ester (FAEE) on Abeta (1-42) induced modulation in phospholipid asymmetry in the synaptosomal membranes. Pretreatment of synaptosomes with D609 and FAEE significantly protected Abeta (1-42)-induced loss of phospholipid asymmetry in synaptosomal membranes. Our results suggest that D609 and FAEE exert protective effects against Abeta (1-42) induced apoptosis. The increase in intracellular Ca(2+) might not be the sole cause for the loss of flippase activity. Rather, other mechanisms that could modulate the function of flippase might be important in the modulation of phospholipid asymmetry. The results of this study are discussed with relevance to neuronal loss in the AD brain.

PMID: 15955457 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/15955457
Full text: http://www.chem.uky.edu/research/butterfield/dab_pdfs/Abdul -Mohmmad Abdul and Butterfield 2005 Biochim Biophys Acta 1741 140-148.pdf


What is Ferulic acid?
Pure ferulic acid is a yellowish powder. Ferulic acid belong to the family of hydroxycinnamic acid. The chemical structure of ferulic acid is very similar to that of curcumin...
http://www.phytochemicals.info/phytochemicals/ferulic-acid.php


Ferulic Acid Protects Against Alzheimer’s
Ferulic Acid is found in our old friend the blueberry and other foods...
http://www.antioxidants-anti-aging-super-foods.com/ferulic-acid.html


Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid.
Br J Pharmacol. 2001 May;133(1):89-96.
Yan JJ, Cho JY, Kim HS, Kim KL, Jung JS, Huh SO, Suh HW, Kim YH, Song DK.

Department of Pharmacology, College of Medicine, Institute of Natural Medicine, Hallym University, Chunchon, 200-702, S. Korea.
Abstract

1. beta-Amyloid peptide (A beta), a 39 -- 43 amino acid peptide, is believed to induce oxidative stress and inflammation in the brain, which are postulated to play important roles in the pathogenesis of Alzheimer's disease. Ferulic acid is an antioxidant and anti-inflammatory agent derived from plants; therefore, the potential protective activity of ferulic acid against A beta toxicity in vivo was examined. 2. Mice were allowed free access to drinking water (control) or water containing ferulic acid (0.006%). After 4 weeks, A beta 1-42 (410 pmol) was administered via intracerebroventricular injection. 3. Injection of control mice with A beta 1-42 impaired performance on the passive avoidance test (35% decrease in step-through latency), the Y-maze test (19% decrease in alternation behaviour), and the water maze test (32% decrease in percentage time in platform-quadrant). In contrast, mice treated with ferulic acid prior to A beta 1-42 administration were protected from these changes (9% decrease in step-through latency; no decrease in alternation behaviour; 14% decrease in percentage time in platform-quadrant). A beta 1-42 induced 31% decrease in acetylcholine level in the cortex, which was tended to be ameliorated by ferulic acid. 4. In addition, A beta 1-42 increased immunoreactivities of the astrocyte marker glial fibrillary acidic protein (GFAP) and interleukin-1 beta (IL-1 beta) in the hippocampus, effects also suppressed by pretreatment with ferulic acid. 5. Administration of ferulic acid per se unexpectedly induced a transient and slight increase in GFAP and IL-1 beta immunoreactivity in the hippocampus on day 14, which returned to basal levels on day 28. A slight (8%) decrease in alternation behaviour was observed on day 14. 6. These results demonstrate that long-term administration of ferulic acid induces resistance to A beta 1-42 toxicity in the brain, and suggest that ferulic acid may be a useful chemopreventive agent against Alzheimer's disease.

PMID: 11325798 [PubMed]PMCID: PMC1572763
http://www.ncbi.nlm.nih.gov/pubmed/11325798


Ferulic Acid: an intriguing new supplement with some unusual antioxidant properties
The Delano Report

* Anti-aging
* Diabetes
* Cardiovascular disease
* Cancer
* Neuroprotection (Alzheimer’s, cognitive decline, macular degeneration)
* Bone degeneration (osteoporosis)
* Immunity
* Athletic performance
* Safety and dosage: A commonly recommended dose is 250 mg twice per day
http://delano.com/blog/?p=154

EFFECT OF ANM176TM CONTAINING FERULIC ACID AND GARDEN ANGELICA EXTRACT ON ALZHEIMER´S DISEASE

S. Nakamura, K. Sasaki
Rakuwakai Otowa Hospital, Neurology, Kyoto, Japan, 2Kinoko Espoir Hospital, Psychiary, Kasoka, Japan

Background: Ferulic acid has been shown to prevent amyloid β (Aβ) induced neurotoxiciy in rat hippocampus and also to protect rats against the impairment of inhibitory avoidance caused by Aβ, scopolamine or cycloheximide.
Methods: We administered ANM176TM containing ferulic acid and garden angelica extract to 143 Alzheimer disease (AD) patients for 9 months. Their cognitive function was measured by Japanese version of Alzheimer's disease assessment scale-cognitive subscale (ADAS-Jcog) or mini-mental scale examination (MMSE). ANM176TM was supplied by the courtesy of Scigenic Co., Korea.
Findings: The change of ADAS-Jcog score in patients treated with ANM176TM for 9 months lessened, when compared with the previously reported change of ADAS-Jcog score in the natural course of AD. The decline of cognitive function was suppressed significantly more remarkably after 9 months in AD patients with ADAS-Jcog score < 20 at onset than those with score ≥30, or in those with MMSE score ≥24 at onset than those with score ≤10. AD cases with early-onset (< 65 years old) after 6 months exhibited significantly greater worsening than those with late-onset (≥65 years old) after 9 months when measured with ADAS-Jcog. ANM176TM attenuated worsening in ADAS-Jcog score after 6 months more effectively when administered alone, compared with those accompanied with donepezil treatment. ANM176TM was well tolerated without any noticeable side effect.
Interpretation: Present results suggest ANM176TM could be recommended for relatively mild AD patients with late-onset without donepezil treatment.
http://www.kenes.com/adpd2009/posters/Abstract1138.htm
PDF of paper: http://www.kenes.com/adpd2009/cd/pdf/316.pdf

Effect of ferulic acid and Angelica archangelica extract on behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies
Takemi Kimura1,*, Hideki Hayashida2, Masako Murata1, Junichi Takamatsu1
Article first published online: 28 JAN 2011
Japan Geriatrics Society

Angelica archangelica;behavioral and psychological symptoms of dementia;dementia with Lewy bodies;ferulic acid;frontotemporal lobar degeneration
Aim:  The behavioral and psychological symptoms of dementia place a heavy burden on caregivers. Antipsychotic drugs, though used to reduce the symptoms, frequently decrease patients' activities of daily living and reduce their quality of life. Recently, it was suggested that ferulic acid is an effective treatment for behavioral and psychological symptoms. We have also reported several patients with dementia with Lewy bodies showing good responses to ferulic acid and Angelica archangelica extract (Feru-guard). The present study investigated the efficacy of Feru-guard in the treatment of behavioral and psychological symptoms in frontotemporal lobar degeneration and dementia with Lewy bodies.

Methods:  We designed a prospective, open-label trial of daily Feru-guard (3.0 g/day) lasting 4 weeks in 20 patients with frontotemporal lobar degeneration or dementia with Lewy bodies. Behavioral and psychological symptoms of dementia were assessed at baseline and 4 weeks after the start of treatment, using the Neuropsychiatric Inventory. The Neuropsychiatric Inventory scores were analyzed using the Wilcoxon rank sum test.

Results:  Treatment with Feru-guard led to decreased scores on the Neuropsychiatric Inventory in 19 of 20 patients and significantly decreased the score overall. The treatment also led to significantly reduced subscale scores on the Neuropsychiatric Inventory (“delusions”, “hallucinations”, “agitation/aggression”, “anxiety”, “apathy/indifference”, “irritability/lability” and “aberrant behavior”). There were no adverse effects or significant changes in physical findings or laboratory data.

Conclusion:  Feru-guard may be effective and valuable for treating the behavioral and psychological symptoms of dementia in frontotemporal lobar degeneration and dementia with Lewy bodies. Geriatr Gerontol Int 2011; 11

DOI: 10.1111/j.1447-0594.2010.00687.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1447-0594.2010.00687.x/abstract


Protective effect of Z-ligustilide against amyloid beta-induced neurotoxicity is associated with decreased pro-inflammatory markers in rat brains.
Pharmacol Biochem Behav. 2009 Jun;92(4):635-41. Epub 2009 Mar 24.
Kuang X, Du JR, Chen YS, Wang J, Wang YN.

State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu 610041, China.
Abstract

Neuroinflammatory responses induced by accumulation and aggregation of beta-amyloid (Abeta) peptide are mainly involved in Alzheimer's disease (AD) pathogenesis. Z-ligustilide (LIG), a novel neuroprotectant against ischemic stroke, was reported to have significant anti-inflammatory effects via inhibition of TNF-alpha production and bioactivity. The present study investigated the effect of LIG on AD-like cognitive impairment and neuropathological and neuroinflammatory changes induced by bilateral intracerebroventricular injections of Abeta(25-35) at a dose of 50 nmol/rat. Rats received oral administration of 40 mg/kg LIG or volume-matched vehicle 1 h before Abeta(25-35) treatment then once daily for 15 days. Morris water maze was used to detect the cognitive dysfunction induced by Abeta(25-35). Compared to the sham-operated rats, Abeta(25-35) injection significantly prolonged the mean escape latency in vehicle-treated rats in the Morris water maze test (p < 0.01) and increased both AD-related neuropathological signs (i.e., Abeta, amyloid precursor protein, and phosphorylated Tau immunoreactivity) and pro-inflammatory mediators (i.e., TNF-alpha and activated NF-kappaB) in the prefrontal cortex and CA1 subregion of the hippocampus. And these neurotoxic effects of Abeta(25-35) were significantly ameliorated with LIG treatment (p < 0.01 vs. vehicle-treated group). The present data suggest that LIG modulates TNF-alpha-activated NF-kappaB signaling pathway with respect to its protective effect against Abeta(25-35)-induced neurotoxicity. LIG would be a potential candidate for further preclinical study aimed at the prevention and treatment of cognitive deficits in AD.

PMID: 19324070 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/19324070

... I want to introduce you to a new alternative medicine originally formulated by a Chinese gentleman, Xue Kai and his son, Xue ji, in Ming dynasty China in 1555 as a remedy for restlessness and agitation in children. The formulation is called Yi-Gan San (YGS), later adapted by the Japanese and called Yokukansan (YKS) around the 5th century.  For brevity I will usually refer to the Japanese version (YKS) as it has virtually all the accessible research. The formulation of YGS and also YKS includes a mixture of dried herbs: 4 g of Atractylodis lancea rhizome, 4g of Poria, 3 g of Cnidii rhizome [Ferulic acid is a component of Cnidii], 3 g of Angelicae radix, 2 g of Bupleuri radix, 1.5 g of Glycyrrhizae radix and 3 g of Uncariae uncis cum ramulus. The recommended dose is: 2,5 grams of YGS/YKS powder (1.08 g extract) 3x/day. In Japan, YKS has been approved by the Ministry of Health, Labour and Welfare as prescriptions covered under the National health Insurance plan. It is widely reported that the benefits of YGS/YKS are probably attributable to the formulation as a whole, rather than to the individual compounds...

http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/4384001397



Pilot study of pharmacological treatment for frontotemporal dementia: effect of Yokukansan on behavioral symptoms.
Psychiatry Clin Neurosci. 2010 Apr;64(2):207-10.
Kimura T, Hayashida H, Furukawa H, Takamatsu J.
Source

Division of Clinical Research, National Hospital Organization Kikuchi Hospital, 208 Fukuhara, Koshi, Kumamoto 861-1116, Japan. tkimura@kikuti.hosp.go.jp
Abstract

The aim of the present study was to investigate the efficacy of Yokukansan in improving behavioral symptoms of frontotemporal dementia. This study was a prospective, open-label trial of daily Yokukansan for 4 weeks in 20 frontotemporal dementia patients. Yokukansan treatment was found to significantly improve scores for the Neuropsychiatric Inventory and the Stereotypy Rating Inventory. No adverse effects or significant changes in physical findings and laboratory data occurred except for hypokalemia in two cases. The results indicate that Yokukansan can alleviate the behavioral symptoms of frontotemporal dementia. (The clinical trial registration number is UMIN000002704).

PMID:20447015 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/20447015

Five cases of frontotemporal dementia with behavioral symptoms improved by Yokukansan
Kimura T, Hayashida H, Furukawa H, Takamatsu J.
Psychogeriatrics Volume 9, Issue 1, pages 38–43, March 2009 (Japanese Psychogeriatric Society)
Article first published online: 27 MAR 2009

Abstract

Herein, we present five cases with frontotemporal dementia whose behavioral symptoms were improved by Yokukansan, a traditional Japanese medicine (Kampo). All five patients were prescribed Yokukansan (7.5 g/day) to reduce their symptoms. The patients' symptoms were evaluated comprehensively using the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI) before and 4 weeks after Yokukansan treatment. The mean (± SD) scores on the NPI and the SRI before treatment were 55.6 ± 5.4 and 22.2 ± 6.5, respectively. After treatment, these scores were 30.0 ± 7.8 and 11.6 ± 7.5, respectively. Yokukansan was effective for the treatment of clinical symptoms in all five patients without adverse effects and significant changes in laboratory data. Although antipsychotic drugs have been used to control behavioral symptoms, their associated adverse effects frequently impact on the activities of daily living and quality of life of treated patients. The present cases suggest significant improvement of behavioral symptoms in frontotemporal dementia with Yokukansan treatment, leading to probable benefit of the use of Yokukansan in individuals with frontotemporal dementia.
DOI: 10.1111/j.1479-8301.2008.00261.x
Full text: http://onlinelibrary.wiley.com/doi/10.1111/j.1479-8301.2008.00261.x/full

Substance in Tangerines Fights Obesity and Protects Against Heart Disease, Research Suggests

ScienceDaily (Apr. 6, 2011) — New research from The University of Western Ontario has discovered a substance in tangerines not only helps to prevent obesity, but also offers protection against type 2 diabetes, and even atherosclerosis, the underlying disease responsible for most heart attacks and strokes... "The Nobiletin-treated mice were basically protected from obesity. And in longer-term studies, Nobiletin also protected these animals from atherosclerosis, the buildup of plaque in arteries, which can lead to a heart attack or stroke. This study really paves the way for future studies to see if this is a suitable treatment for metabolic syndrome and related conditions in people."

http://www.sciencedaily.com/releases/2011/04/110406161030.htm


Nobiletin Attenuates VLDL Overproduction, Dyslipidemia, and Atherosclerosis in Mice With Diet-Induced Insulin Resistance.
Diabetes. 2011 Apr 6.
Mulvihill EE, Assini JM, Lee JK, Allister EM, Sutherland BG, Koppes JB, Sawyez CG, Edwards JY, Telford DE, Charbonneau A, St-Pierre P, Marette A, Huff MW.

Vascular Biology, Robarts Research Institute, London, Ontario, Canada.
Abstract

OBJECTIVE Increased plasma concentrations of apolipoprotein B100 often present in patients with insulin resistance and confer increased risk for the development of atherosclerosis. Naturally occurring polyphenolic compounds including flavonoids have antiatherogenic properties. The aim of the current study was to evaluate the effect of the polymethoxylated flavonoid nobiletin on lipoprotein secretion in cultured human hepatoma cells (HepG2) and in a mouse model of insulin resistance and atherosclerosis. RESEARCH DESIGN AND METHODS Lipoprotein secretion was determined in HepG2 cells incubated with nobiletin or insulin. mRNA abundance was evaluated by quantitative RT-PCR, and Western blotting was used to demonstrate activation of cell signaling pathways. In LDL receptor-deficient mice (Ldlr(-/-)) fed a Western diet supplemented with nobiletin, metabolic parameters, gene expression, fatty acid oxidation, glucose homeostasis, and energy expenditure were documented. Atherosclerosis was quantitated by histological analysis. RESULTS In HepG2 cells, activation of mitogen-activated protein kinase-extracellular signal-related kinase signaling by nobiletin or insulin increased LDLR and decreased MTP and DGAT1/2 mRNA, resulting in marked inhibition of apoB100 secretion. Nobiletin, unlike insulin, did not induce phosphorylation of the insulin receptor or insulin receptor substrate-1 and did not stimulate lipogenesis. In fat-fed Ldlr(-/-) mice, nobiletin attenuated dyslipidemia through a reduction in VLDL-triglyceride (TG) secretion. Nobiletin prevented hepatic TG accumulation, increased expression of Pgc1α and Cpt1α, and enhanced fatty acid β-oxidation. Nobiletin did not activate any peroxisome proliferator-activated receptor (PPAR), indicating that the metabolic effects were PPAR independent. Nobiletin increased hepatic and peripheral insulin sensitivity and glucose tolerance and dramatically attenuated atherosclerosis in the aortic sinus. CONCLUSIONS Nobiletin provides insight into treatments for dyslipidemia and atherosclerosis associated with insulin-resistant states.

PMID: 21471511 [PubMed]
http://www.ncbi.nlm.nih.gov/pubmed/21471511

Type-2 diabetes linked to autoimmune reaction in study
APRIL 17, 2011
Stanford School of Medicine
...Nearly all type-2 diabetes drugs marketed today are designed to control a patient’s high blood sugar levels — a symptom of the body’s inability to respond properly to insulin. However, the researchers found that anti-CD20, which targets and eliminates mature B cells, could completely head off the development of type-2 diabetes in laboratory mice prone to the disorder and restore their blood sugar levels to normal. The researchers believe that insulin resistance arises when the B cells and other immune cells react against the body’s own tissues... Several years ago, Daniel and Shawn Winer began to speculate that different types of immune cells, including T cells and B cells, can cause inflammation in the fatty tissue that surrounds and cushions organs in the body. This inflammation occurs in mice fed a high-fat, high-calorie diet when the rapidly growing fat cells outstrip their blood supply and begin to die. (It’s also seen in humans with type-2 diabetes.) The dying cells spew their contents, and immune system cells called macrophages are summoned to clean up the mess...
http://med.stanford.edu/ism/2011/april/engleman.html

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Periodontal (gum) disease

http://alzheimers.infopop.cc/eve/forums/a/tpc/f/762104261/m/4211047603?r=9701028603#9701028603

Gum Inflammation Linked to Alzheimer's Disease

ScienceDaily (Aug. 4, 2010) — NYU dental researchers have found the first long-term evidence that periodontal (gum) disease may increase the risk of cognitive dysfunction associated with Alzheimer's disease in healthy individuals as well as in those who already are cognitively impaired... "The research suggests that cognitively normal subjects with periodontal inflammation are at an increased risk of lower cognitive function compared to cognitively normal subjects with little or no periodontal inflammation"...
http://www.sciencedaily.com/releases/2010/08/100803112811.htm

New York University (2010, August 4). Gum inflammation linked to Alzheimer's disease. ScienceDaily. Retrieved August 7, 2011

But what is the connection? Could it be the same as the possible connection between an H.pylori infection of the stomach and AD: excess TNF-alpha production?


While looking up an article about resveratrol, I stumbled across this one. What I found interesting is that these substances may decrease the influence of TNF-alpha (which is what drugs like Enbrel block).

Study on Effects of Resveratrol and Quercetin on Inflammation and Insulin Resistance
ScienceDaily (Dec. 23, 2010) — A study was carried out to examine the extent to which quercetin and trans-resveratrol (RSV) prevented inflammation or insulin resistance in primary cultures of human adipocytes treated with tumor necrosis factor-a (TNF-a) -- an inflammatory cytokine elevated in the plasma and adipose tissue of obese, diabetic individuals. Cultures of human adipocytes were pretreated with quercetin and trans-RSV followed by treatment with TNF-a. Subsequently, gene and protein markers of inflammation and insulin resistance were measured. The authors report that quercetin, and to a lesser extent trans-RSV, attenuated the TNF-a-induced expression of inflammatory genes...
http://www.sciencedaily.com/releases/2010/12/101223104042.htm


Inflammatory cytokines, adiponectin, insulin resistance and metabolic control after periodontal intervention in patients with type 2 diabetes and chronic periodontitis.
Sun WL, Chen LL, Zhang SZ, Wu YM, Ren YZ, Qin GM.
Source
Department of Oral Medicine and Periodontology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, China.
Intern Med. 2011;50(15):1569-74. Epub 2011 Aug 1.

Abstract
Objective To evaluate the effects of periodontal intervention on inflammatory cytokines, adiponectin, insulin resistance (IR), and metabolic control and to investigate the relationship between type 2 diabetes mellitus (T2DM) and moderately poor glycemic control and chronic periodontitis. Methods and Patients A total of 190 moderately poorly controlled (HbA1c between 7.5% and 9.5%) T2DM patients with periodontitis were randomly divided into two groups according to whether they underwent periodontal intervention: T2DM-NT and T2DM-T group. The levels of serum adiponectin, C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), lipid profile, glucose, insulin, homeostasis model of assessment - insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) were measured at baseline and after 3 months. Results The levels of clinical periodontal variables, the probing depth, attachment loss, bleeding index, and plaque index were improved significantly in T2DM-T group after 3 months compared to T2DM-NT group (all p<0.01). After 3 months, the serum levels of hsCRP, TNF-α, IL-6, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS) and HOMA-IR index decreased, and adiponectin was significantly increased in T2DM-T group compared to those in the T2DM-NT group (p<0.05 or p<0.01). Conclusion Periodontal intervention can improve glycemic control, lipid profile and IR, reduce serum inflammatory cytokine levels and increase serum adiponectin levels in moderately poorly controlled T2DM patients.

PMID: 21804283
http://www.ncbi.nlm.nih.gov/pubmed/21804283

Neurology
Issue: Volume 74(14), 6 April 2010, pp 1157-1158

"We agree with Dr. Kamer that periodontitis probably plays an important role in disease progression in AD. Periodontitis is a good example of a peripheral chronic infectious disease known to be associated with the production of systemic proinflammatory cytokines. including TNF-[alpha], interleukin-6, and interleukin-1[beta].5"

SYSTEMIC INFLAMMATION AND DISEASE PROGRESSION IN ALZHEIMER DISEASE
Kamer, Angela R.
Author Information
New York, NY

 
To the Editor:
 
We read the article by Holmes et al.1 with interest. Holmes et al.2 continue their pioneering work and now address a significant and highly controversial question: Does peripheral inflammation contribute to the progression of Alzheimer disease (AD)?...
[ NEED link ]

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Bexarotene

Drug Quickly Reverses Alzheimer's Symptoms in Mice
ScienceDaily (Feb. 9, 2012) — Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer's disease. The researchers' findings, published in the journal Science, show that use of a drug in mice appears to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer's. The results point to the significant potential that the medication, bexarotene, has to help the roughly 5.4 million Americans suffering from the progressive brain disease...
http://www.sciencedaily.com/releases/2012/02/120209144005.htm

ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models.
Paige E. Cramer, John R. Cirrito, Daniel W. Wesson, C. Y. Daniel Lee, J. Colleen Karlo, Adriana E. Zinn, Brad T. Casali, Jessica L. Restivo, Whitney D. Goebel, Michael J. James, Kurt R. Brunden, Donald A. Wilson, and Gary E. Landreth.
Science, 9 February 2012 DOI: 10.1126/science.1217697

Abstract

Alzheimer's disease is associated with impaired clearance of β-amyloid from the brain, a process normally facilitated by apolipoprotein E (ApoE). ApoE expression is transcriptionally induced through the action of the nuclear receptors peroxisome proliferator activated receptor (PPARγ) and liver X receptors (LXR) in coordination with retinoid X receptors (RXR). Oral administration of the RXR agonist, bexarotene, to a murine model of Alzheimer's disease resulted in enhanced clearance of soluble Aβ within hours in an apoE-dependent manner. Aβ plaque area was reduced >50% within just 72 hours. Furthermore, bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function. Thus, RXR activation stimulates physiological Aβ clearance mechanisms, resulting in the very rapid reversal of a broad range of Aβ-induced deficits.
http://www.sciencemag.org/content/early/2012/02/08/science.1217697

Wikipedia:
Bexarotene (tradenamed Targretin) is an oral antineoplastic agent indicated by the FDA (in 2000) for cutaneous T cell lymphoma.[1] It has been used off-label for lung cancer,[2] breast cancer, and Kaposi's sarcoma.
http://en.wikipedia.org/wiki/Bexarotene


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Trehalose a.k.a mycose or tremalose

Wikipedia: Trehalose: a natural alpha-linked disaccharide formed by an α,α-1,1-glucoside bond between two α-glucose units.



Interestingly, one major source of trehalose in the United States is Brooklyn Premium Corp., Brooklyn, New York, perhaps better known for their "Sweet’N Low" sugar substitute.  Their product is called NeuroCoat™.

[ EDIT NOTE:  Need MUCH more information about this topic.]

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Updated: December 25, 2010
Inception: June 5, 2006