******************************************************************************************** Treating
protein folding diseases
"Preventing aggregation is therefore a primary therapeutic target, but
there is more than one stage that can be targeted. Strategies so far
have focused on disrupting polymerization and fibril aggregation. These
include using low-molecular-weight substances such as congo red dye,
the antibiotic rifampicin, peptides that bind to amyloid-b
peptide and drugs that chelate metals such as copper and zinc, which
themselves accelerate amyloid-b deposition. Indeed, interim results
from a placebo-controlled trial of the antibiotic iodochlorhydroxyquin
(Clioquinol), which chelates these metals in vitro, showed slowing of
cognitive decline in the most severely affected of 32 Alzheimer's
disease patients studied." http://www.nature.com/horizon/proteinfolding/background/treating.html
Vascular cognitive impairment
Journal of Neurology, Neurosurgery, and Psychiatry
2005;76(suppl_5):v35-v44; doi:10.1136/jnnp.2005.082313
"Regulatory bodies, which increasingly determine what may be done and
to whom, have a tendency to adhere rigidly to published data. If data
exist only for advanced disease, then expensive drugs may only be
available for advanced disease, at least within guidelines. This
important early stage is termed vascular cognitive impairment (VCI).
The importance of VCI lies in the fact that vascular disease is the
largest single identifiable risk factor for dementia apart from age and
the only one currently treatable. Indeed, the concept can be taken
further; while the prevention of progression of VCI is analogous to
secondary prevention, primary prevention requires the recognition of
the presence of risk factors in a susceptible host, termed
"brain-at-risk"." http://jnnp.bmj.com/cgi/content/full/76/suppl_5/v35
Aqueous Dissolution of Alzheimer's
Disease Abeta Amyloid Deposits by Biometal Depletion
J Biol Chem, Vol. 274, Issue 33, 23223-23228, August 13, 1999
"Zn(II) and Cu(II) precipitate Abeta in vitro into insoluble
aggregates that are dissolved by metal chelators. We now report
evidence that these biometals also mediate the deposition of
Abeta amyloid in Alzheimer's disease, since the solubilization of
Abeta from post-mortem brain tissue was significantly increased
by the presence of chelators, EGTA,
N,N,N',N'-tetrakis(2-pyridyl-methyl) ethylene diamine, and
bathocuproine. Efficient extraction of Abeta also required Mg(II)
and Ca(II). The chelators were more effective in extracting Abeta
from Alzheimer's disease brain tissue than age-matched controls,
suggesting that metal ions differentiate the chemical architecture of
amyloid in Alzheimer's disease. Agents that specifically chelate copper
and zinc ions but preserve Mg(II) and Ca(II) may be of therapeutic
value in Alzheimer's disease." http://www.jbc.org/cgi/content/full/274/33/23223
Strategies to Diminish the Ab Load in
Alzheimer’s Disease
Curr. Med. Chem. – Central Nervous System Agents, 2005, 5, 15-28
"Abstract: Striking advances have been made in recent years toward
potential therapies for Alzheimer’s disease. Alzheimer’s disease, which
is the leading cause of dementia in the elderly, is pathologically
defined by the presence of amyloid plaques, composed of the
amyloid-beta protein, and neurofibrillary tangles. The amyloid
pathology has been associated with decreased synaptic plasticity and
neurodegeneration, thereby explaining the visibly decreased cognitive
function and evident dementia. Subsequently, a large number of studies
have been launched, which attempt to disrupt the progression
from Ab aggregation to plaque formation. These studies have involved
the use of beta-sheet breakers, secretase inhibition, immunotherapy and
anti-inflammatories, the most notable findings of which are discussed
in this review." http://www.bentham.org/cmccnsa/sample/cmccnsa5-1/0004T.pdf
Astonishing Memory Pill (Ginkgo)
October 22, 2000 - Excerpts from Miracle
Cures By Jean Carper
"The plant's reputed most active chemicals, the ginkgolides, are
generally extracted from the leaves and turned into tablets of various
potency. These potent ginkgolides are unique to the ginkgo tree and are
not found anywhere else in nature."
"In a large, very tightly structured study, published in 1996, German
investigators at the Free University, Berlin, observed the use of
ginkgo on 222 outpatients at forty-one study centers around the
country. The subjects, all over age fifty-five, had been diagnosed with
mild to moderate Alzheimer-type dementia or dementia caused by a series
of mini strokes, known medically as multi-infarcts. For six months the
patients were given either a dummy pill or a daily dose of 240
milligrams of standardized ginkgo biloba extract (EGb 761), taken twice
a day before meals. Undeniably, those getting ginkgo did much better." http://www.vitamin-resource.com/health/detail.cfm?id=145
Natural options for Alzheimer’s
Disease treatment - Alternatives to Alzheimer's Medication
While scientists have not fully determined the actual causes of
Alzheimer’s disease, a number of treatment options have been proposed
or tried over the years. Although much more research needs to be done
in order to find out the role of these supplements in Alzheimer's
disease treatment, I think it is appropriate to give them a try since
this condition currently has no cure or effective treatment. You are
not likely to find this information in any official Alzheimer's disease
association or Alzheimer's foundation. Some natural options for
Alzheimer's disease treatment or prevention include (discuss with your
doctor first)
******************************************************************************************** Curcumin
Definitions: Free
Dictionary Wikipedia
"Curcumin is the principal curcuminoid of the Indian curry spice
turmeric. The curcuminoids are polyphenols and are responsible for the
yellow color of turmeric. Curcumin can exist in at least two tautomeric
forms, keto and enol. The enol form is more energetically stable in the
solid phase and in solution"
"Curcumin is known for its antitumor, antioxidant, anti-amyloid and
anti-inflammatory properties. Anti-inflammatory properties may be due
to inhibition of eicosanoid biosynthesis."
Curcumin Inhibits Formation of
Amyloid {beta} Oligomers and Fibrils,
Binds Plaques, and Reduces Amyloid in Vivo
J. Biol. Chem., Vol. 280, Issue 7, 5892-5901, February 18, 2005
"Alzheimer's disease (AD) involves amyloid {beta} (A{beta})
accumulation, oxidative damage, and inflammation, and risk is reduced
with increased antioxidant and anti-inflammatory consumption. The
phenolic yellow curry pigment curcumin has potent anti-inflammatory and
antioxidant activities and can suppress oxidative damage, inflammation,
cognitive deficits, and amyloid accumulation. Since the molecular
structure of curcumin suggested potential A{beta} binding, we
investigated whether its efficacy in AD models could be explained by
effects on A{beta} aggregation... When fed to aged Tg2576 mice with
advanced amyloid accumulation, curcumin labeled plaques and reduced
amyloid levels and plaque burden. Hence, curcumin directly binds small
{beta}-amyloid species to block aggregation and fibril formation in
vitro and in vivo. These data suggest that low dose curcumin
effectively disaggregates A{beta} as well as prevents fibril and
oligomer formation, supporting the rationale for curcumin use in
clinical trials preventing or treating AD." http://www.jbc.org/cgi/content/full/280/7/5892
A
Potential Role of the Curry Spice
Curcumin in Alzheimer’s Disease
UCLA Dept. of Neurology, Alzheimer’s Disease Research Center
"There is substantial in-vitro data indicating that curcumin has
antioxidant, anti-inflammatory, and anti-amyloid activity. In addition,
studies in animal models of Alzheimer’s disease (AD) indicate a direct
effect of curcumin in decreasing the amyloid pathology of AD. As the
widespread use of curcumin as a food additive and relatively small
short-term studies in humans suggest safety, curcumin is a promising
agent in the treatment and/or prevention of AD. Nonetheless, important
information regarding curcumin bioavailability, safety and
tolerability, particularly in an elderly population is lacking. We are
therefore performing a study of curcumin in patients with AD to gather
this information in addition to data on the effect of curcumin on
biomarkers of AD pathology." http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1702408
also http://www.ingentaconnect.com/content/ben/car/2005/00000002/00000002/art00006?token=004b19a063c1a9a3d332b25757d5c4f6d4e227a677e442f20675d3b7646255c23796d7a3144
An Indian Spice for Alzheimer's?
"Researchers here in the United States have been pursuing clues to the
effects of curcumin, a compound found in the spice turmeric that is
responsible for the yellow color of Indian curry and American mustard.
Studies show that elderly villagers in India appear to have the lowest
rate of Alzheimer's disease in the world. Researchers speculate that
curcumin, which has powerful antioxidant and anti-inflammatory
properties might play a role, because Indians eat turmeric with almost
every meal." http://www.drweil.com/drw/u/id/QAA72328
Curcumin, the Curry Spice Part 2
"The levels of beta-amyloid in AD mice that were given low doses of
curcumin were decreased by around 40% in comparison to those AD mice
that were not treated with curcumin. In addition, low doses of curcumin
also caused a 43% decrease in the so-called "plaque burden" that these
beta-amyloids have on the brains of AD mice. Surprisingly, those AD
mice that received high doses of curcumin did not show any decreases in
beta-amyloid levels or plaque burden in comparison with untreated mice.
While the exact reason for this finding is not yet clear, the results
of it are intriguing: low doses of
curcumin were actually more effective than high doses in
combating the neurodegenerative process of AD." http://www.stanford.edu/group/hopes/treatmts/curcumin/ai2.html
Curcumin has potent
anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in
vitro.
"Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the
formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the
destabilization of preformed fAbeta in the central nervous system,
would be attractive therapeutic targets for the treatment of
Alzheimer's disease (AD). We reported previously that
nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit
fAbeta formation from Abeta(1-40) and Abeta(1-42) and destabilize
preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro..." http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=14994335
Spice Protects Brain Cells, Could
Prevent Alzheimer's Disease
"In their study, researchers exposed rat brain cells to various
concentrations of curcumin, then analyzed the cells 24 hours later.
Indeed, they found HO-1 as well as two other protective enzymes.
However, higher concentrations of curcumin caused substantial cell
damage -- with no increase in the protective HO-1 protein, she reports." http://www.webmd.com/alzheimers/news/20040419/hot-tip-curry-may-protect-aging-brain
The Curry Spice Curcumin Reduces
Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse
The Journal of Neuroscience, November
1, 2001, 21(21):8370-8377
"To evaluate whether it could affect Alzheimer-like pathology in the
APPSw mice, we tested a low (160 ppm) and a high dose of dietary
curcumin (5000 ppm) on inflammation, oxidative damage, and plaque
pathology. Low and high doses of curcumin significantly lowered
oxidized proteins and interleukin-1beta , a proinflammatory cytokine
elevated in the brains of these mice. With low-dose but not high-dose
curcumin treatment, the astrocytic marker GFAP was reduced, and
insoluble beta -amyloid (Abeta ), soluble Abeta , and plaque burden
were significantly decreased by 43-50%. However, levels of amyloid
precursor (APP) in the membrane fraction were not reduced. Microgliosis
was also suppressed in neuronal layers but not adjacent to plaques. In
view of its efficacy and apparent low toxicity, this Indian spice
component shows promise for the prevention of Alzheimer's disease." http://www.jneurosci.org/cgi/content/abstract/21/21/8370
UCLA/VA Study Finds Chemical Found in
Curry May Help Immune System Clear Amyloid Plaques Found in Alzheimer’s
Disease
Date: October 3, 2006
"UCLA/VA researchers found that curcumin — a chemical found in curry
and turmeric — may help the immune system clear the brain of amyloid
beta, which form the plaques found in Alzheimer's disease. Published in
the Oct. 9 issue of the Journal of Alzheimer's Disease, the early
laboratory findings may lead to a new approach in treating Alzheimer's
disease by enhancing the natural function of the immune system using
curcumin, known for its anti-inflammatory and anti-oxidant properties." http://newsroom.ucla.edu/page.asp?RelNum=7366
also, http://www.hbri.org/NewsandEvents_PR_10-3-06.htm
Molecular Orbital Basis for Yellow
Curry Spice Curcumin's Prevention of Alzheimer's Disease
"It is demonstrated by using high-level ab initio computations that the
yellow curcumin pigment,
bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione, in the east Indian
root plant turmeric (Curcuma longa) exhibits unique charge and bonding
characteristics that facilitate penetration into the blood-brain
barrier and binding to amyloid-β (Aβ). Alzheimer's disease is caused by
Aβ accumulation in the brain cells combined with oxidative stress and
inflammation. Consistent with the recent experimental work by Cole and
co-workers (Yang, F., et al. J. Biol. Chem. 2004, 280, 5892-5901) that
demonstrates curcumin pigment's binding ability to Aβ both in vivo and
in vitro, it is shown here that curcumin possesses suitable charge and
bonding features to facilitate the binding to Aβ." http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i10/abs/jf0603533.html
Spice
Up Your Brain Preserve brain function with spicy
foods.
By PsychologyToday.com
"About a tablespoon of curry a day, or 200 mg of curcumin, does the
trick, says Dr. Sally Frautschy, associate professor of medicine at
UCLA. “I eat curry at least 4 times a week,” she reports."
Curcuminoids as potential new
iron-chelating agents: spectroscopic, polarographic and potentiometric
study on their Fe(III) complexing ability
Authors: Borsari M.; Ferrari E.; Grandi R.; Saladini M.1
Source: Inorganica Chimica Acta, Volume 328, Number 1, 30 January 2002
, pp. 61-68(8)
Marco Borsari, Erika Ferrari, Romano Grandi and Monica Saladini
Department of Chemistry, University of Modena and Reggio Emilia, Via
Campi 183, 41100 Modena, Italy
Abstract
"The pKa values of curcumin and diacetylcurcumin are, here doubtless,
determined by means of spectroscopic and potentiometric measurements,
and the enolic proton is the more acidic one. The interaction of Fe3+
with curcumin and diacetylcurcumin, in water/methanol 1:1 solution,
leads to the formation of the complex species [FeH2CU(OH)2] and
[FeDCU(OH)2] (H2CU and DCU=curcumin or diacetylcurcumin monoanion,
respectively) which prevails near pH 7. At more basic condition the
prevailing species are [FeH2CU(OH)3]− and [FeDCU(OH)3]−, which prevent
metal hydroxide precipitation. 1H NMR data state that the dissociated
β-diketo moiety of the ligands is involved in metal chelation. The pKa
value of the deprotonation reaction is strongly anticipated by the
metal ion, as shown by UV spectral data. The stability constants,
evaluated from potentiometric data, are near to that of
desferrioxamine, which is, by now, the only iron-chelating agent for
clinical use...Curcumin and diacetylcurcumin coordinate Fe(III) through
β-diketone moiety, form stable complexes. The prevailing species at
physiological pH is [FeH2CU(OH)2] whose stability constant is near to
those of iron-sequestering agents for clinical use." http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TG5-44W31SJ-8&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ec04b29401cf941169efb08fb8bb3f70
Curcumin interaction with copper and
iron suggests one possible mechanism of action in Alzheimer's disease
animal models.
J Alzheimers Dis. 2004 Aug;6(4):367-77; discussion 443-9.
Baum L, Ng A.
Department of Medicine and Therapeutics, Chinese University of Hong
Kong, Shatin. lwbaum@cuhk.edu.hk
"Curcumin is a polyphenolic diketone from turmeric. Because of its
anti-oxidant and anti-inflammatory effects, it was tested in animal
models of Alzheimer's disease, reducing levels of amyloid and oxidized
proteins and preventing cognitive deficits. An alternative mechanism of
these effects is metal chelation, which may reduce amyloid aggregation
or oxidative neurotoxicity. Metals can induce Abeta aggregation and
toxicity, and are concentrated in AD brain. Chelators desferrioxamine
and clioquinol have exhibited anti-AD effects. Using spectrophotometry,
we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+
showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at
least two curcumin molecules. The interaction of curcumin with copper
reached half-maximum at approximately 3-12 microM copper and exhibited
positive cooperativity, with Kd1 approximately 10-60 microM and Kd2
approximately 1.3 microM (for binding of the first and second curcumin
molecules, respectively). Curcumin-iron interaction reached
half-maximum at approximately 2.5-5 microM iron and exhibited negative
cooperativity, with Kd1 approximately 0.5-1.6 microM and Kd2
approximately 50-100 microM. Curcumin and its metabolites can attain
these levels in vivo, suggesting physiological relevance. Since
curcumin more readily binds the redox-active metals iron and copper
than redox-inactive zinc, curcumin might exert a net protective effect
against Abeta toxicity or might suppress inflammatory damage by
preventing metal induction of NF-kappaB."
Curcumin stimulates proliferation of
embryonic neural progenitor cells and neurogenesis in the adult
hippocampus.
Kim SJ, Son TG, Park HR, Park M, Kim MS, Kim HS, Chung HY, Mattson MP,
Lee J.
Pharmacy, Pusan National University, Busan 609-735.
"Curcumin is a natural phenolic component of yellow curry spice, which
is used in some cultures for the treatment of diseases associated with
oxidative stress and inflammation. Curcumin has been reported capable
of preventing the death of neurons in animal models of
neurodegenerative disorders, but its possible effects on developmental
and adult neuroplasticity are unknown. In the present study, we
investigated the effects of curcumin on mouse multi-potent neural
progenitor cells (NPC) and adult hippocampal neurogenesis. Curcumin
exerted biphasic effects on cultured NPC - low concentrations
stimulated cell proliferation, whereas high concentrations were
cytotoxic. Curcumin activated extracellular signal regulated kinases
(ERKs) and p38 kinases, cellular signal transduction pathways known to
be involved in the regulation of neuronal plasticity and stress
responses. Inhibitors of ERKs and p38 kinases effectively blocked the
mitogenic effect of curcumin in NPC. Administration of curcumin to
adult mice resulted in a significant increase in the number of
newly-generated cells in the dentate gyrus of hippocampus, indicating
that curcumin enhances adult hippocampal neurogenesis. Our findings
suggest that curcumin can stimulate developmental and adult hippocampal
neurogenesis, a biological activity that may enhance neural plasticity
and repair."
Vitamin D, Curcumin May Help Clear
Amyloid Plaques Found In Alzheimer's Disease
ScienceDaily (July 15, 2009)
"UCLA scientists and colleagues from UC Riverside and the Human
BioMolecular Research Institute have found that a form of vitamin D,
together with a chemical found in turmeric spice called curcumin, may
help stimulate the immune system to clear the brain of amyloid beta,
which forms the plaques considered the hallmark of Alzheimer's disease.
The early research findings, which appear in the July issue of the
Journal of Alzheimer's Disease, may lead to new approaches in
preventing and treating Alzheimer's by utilizing the property of
vitamin D3 — a form of vitamin D — both alone and together with natural
or synthetic curcumin to boost the immune system in protecting the
brain against amyloid beta..." http://www.sciencedaily.com/releases/2009/07/090715131558.htm
MEG VERREES, M.D., and WARREN R. SELMAN, M.D.
Case Western Reserve University, Cleveland, Ohio
"Gait instability, urinary incontinence, and dementia are the signs and
symptoms typically found in patients who have normal pressure
hydrocephalus. Estimated to cause no more than 5 percent of cases of dementia, ...
often is treatable... Magnetic resonance imaging or computed tomography
typically demonstrates ventricular dilation with preservation of the
surrounding brain tissue. ... normal pressure hydrocephalus ... leading
to an increase in ventricular size and encroachment of enlarged
ventricles on adjacent brain tissue. The pressure exerted ... deforms
white matter tracts, instigating gait abnormalities and incomplete
control of the bladder, as well as difficulties in processing incoming
stimulation and in producing expeditious responses..."
"Normal Pressure Hydrocephalus is a neurological condition which
normally occurs in adults 55-years and older. NPH is an accumulation of
cerebrospinal fluid (CSF) causing the ventricles of the brain to
enlarge, in turn, stretching the nerve tissue of the brain causing a
triad of symptoms."
Paradigm shift in hydrocephalus
research in legacy of Dandy’s pioneering work: rationale for third
ventriculostomy in communicating hydrocephalus
Dan Greitz
Department of Neuroradiology, MR Research Center, Karolinska University
Hospital, Stockholm, Sweden
Abstract
Objective
"This study aims to question the generally accepted cerebrospinal fluid
(CSF) bulk flow theory suggesting that the CSF is exclusively absorbed
by the arachnoid villi and that the cause of hydrocephalus is a CSF
absorption deficit. In addition, this study aims to briefly describe
the new hydrodynamic concept of hydrocephalus and the rationale for
endoscopic third ventriculostomy (ETV) in communicating hydrocephalus."
Critique
"The bulk flow theory has proven incapable of explaining the pivotal
mechanisms behind communicating hydrocephalus. Thus, the theory is
unable to explain why the ventricles enlarge, why the CSF pressure
remains normal and why some patients improve after ETV."
Hydrodynamic concept of hydrocephalus
"Communicating hydrocephalus is caused by decreased intracranial
compliance increasing the systolic pressure transmission into the brain
parenchyma. The increased systolic pressure in the brain distends the
brain towards the skull and simultaneously compresses the
periventricular region of the brain against the ventricles. The final
result is the predominant enlargement of the ventricles and narrowing
of the subarachnoid space. The ETV reduces the increased systolic
pressure in the brain simply by venting ventricular CSF through the
stoma. The patent aqueduct in communicating hydrocephalus is too narrow
to vent the CSF sufficiently." http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1849423
******************************************************************************************** Epigallocatechin
gallate
(EGCG,
Green
Tea
Extract)
Reduction of iron-regulated amyloid
precursor protein and beta-amyloid
peptide by (-)-epigallocatechin-3-gallate in cell cultures:
implications for iron chelation in Alzheimer's disease
J Neurochem. 2006 Apr;97(2):527-36. Epub 2006 Mar 15.
A Fortune in Tea Leaves—Extract
Blocks Amyloid Formation
"31 May 2008. Fortune telling aside, green tea has been touted as a
potential cure for a myriad of conditions, including cancer and
neurodegenerative diseases such as Alzheimer and Parkinson diseases.
Scientific evidence that the brew might work has just become stronger.
In yesterday’s Nature Structural & Molecular Biology, researchers
in Germany report that (-)-epigallocatechin gallate (EGCG), a
polyphenol found in green tea, prevents both amyloid-β (Aβ) and
α-synuclein from forming toxic oligomers. The work suggests that EGCG
works as a generic inhibitor of amyloids, making it a potential lead
for treatments of not only AD and PD but perhaps any amyloidosis." http://www.alzforum.org/new/detail.asp?id=1838
Green Tea Chemical Combined With
Another May Hold Promise for Treatment of Brain Disorders
ScienceDaily (Dec. 6, 2009)
Scientists at Boston Biomedical Research Institute (BBRI) and the
University of Pennsylvania have found that combining two chemicals, one
of which is the green tea component EGCG, can prevent and destroy a
variety of protein structures known as amyloids. Amyloids are the
primary culprits in fatal brain disorders such as Alzheimer's,
Huntington's, and Parkinson's diseases. Their study, published in the
current issue of Nature Chemical Biology (December 2009), may
ultimately contribute to future therapies for these diseases... The
team then exposed the yeast amyloid structures to a combination of the
EGCG and the DAPH-12 and found that all of the amyloid structures broke
apart and dissolved... http://www.sciencedaily.com/releases/2009/12/091203091856.htm
Drug Slows Progression Of Moderate To
Severe Alzheimer's Disease
ScienceDaily (Apr. 4, 2003)
http://www.sciencedaily.com/releases/2003/04/030404072337.htm
"The drug, memantine, slows the mental and physical deterioration of
patients with moderate to severe Alzheimer's disease, according to
Barry Reisberg, M.D., Professor of Psychiatry at NYU School of
Medicine, who led the study. "These patients seem to be declining much
less, about half as much as ordinarily expected, over a six-month
period," says Dr. Reisberg. "This medication will slow down the
otherwise inexorable progress of this disease, and it is remarkably
free of side effects. These are very impressive results. It looks like
this drug really will have an impact on this disease," he says."
******************************************************************************************** Lithium
Here is another take on the use of lithium:
I suggest reading the whole article, but here is an excerpt...
Taking (grey) matters into your own hands
"Hercule Poirot, Agatha Christie's famous fictional detective, had an
amusing quirk in his incessant concern for his "little grey cells." I
thought of Hercule several years ago when I saw the following headline
in an issue of the Lancet: "Lithium-induced increase in human brain
grey matter."
"That may not sound like an earth-shattering piece of news, but it
actually was quite a major discovery. To that point, medical experts
believed that once our brains matured, it was all downhill from then
on. Decades of autopsies, x-rays, and, more recently, brain scans have
repeatedly shown that brains shrink measurably with aging. But
according to their report in the Lancet, Wayne State University
(Detroit) researchers found that lithium has the ability to both
protect and renew brain cells.1 Eight of 10 individuals who took
lithium showed an average 3 percent increase in brain grey matter in
just four weeks.
"Lithium may help to generate entirely new cells too: Another group of
researchers recently reported that lithium also enhances nerve cell DNA
replication.2 DNA replication is a first step in the formation of a new
cell of any type.
"The Wayne State study used high-dose lithium, but I'm certainly not
using that amount myself, nor do I recommend it. Prescription
quantities of lithium just aren't necessary for "everyday" brain cell
protection and re-growth. Studies done years ago have shown that very
low amounts of lithium can also measurably influence brain function for
the better." http://www.tahoma-clinic.com/lithium1.shtml
Inhibition of glycogen synthase
kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo
Proceedings of the National Academy of Sciences of the United States
of America
PNAS | May 10, 2005 | vol. 102 | no. 19 | 6990-6995
"Neurofibrillary tangles composed of hyperphosphorylated, aggregated
tau are a common pathological feature of tauopathies, including
Alzheimer's disease. Abnormal phosphorylation of tau by kinases or
phosphatases has been proposed as a pathogenic mechanism in tangle
formation. To investigate whether kinase inhibition can reduce
tauopathy and the degeneration associated with it in vivo, transgenic
mice overexpressing mutant human tau were treated with the glycogen
synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment
resulted in significant inhibition of GSK-3 activity. Lithium
administration also resulted in significantly lower levels of
phosphorylation at several epitopes of tau known to be
hyperphosphorylated in Alzheimer's disease and significantly reduced
levels of aggregated, insoluble tau. Administration of a second GSK-3
inhibitor also correlated with reduced insoluble tau levels, supporting
the idea that lithium exerts its effect through GSK-3 inhibition.
Levels of aggregated tau correlated strongly with degree of axonal
degeneration, and lithium-chloride-treated mice showed less
degeneration if administration was started during early stages of
tangle development. These results support the idea that kinases are
involved in tauopathy progression and that kinase inhibitors may be
effective therapeutically." http://www.pnas.org/cgi/content/abstract/102/19/6990?ck=nck
Lithium delays progression of
amyotrophic lateral sclerosis.
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2052-7. Epub 2008 Feb 4
"ALS is a devastating neurodegenerative disorder with no effective
treatment. In the present study, we found that daily doses of lithium,
leading to plasma levels ranging from 0.4 to 0.8 mEq/liter, delay
disease progression in human patients affected by ALS. None of the
patients treated with lithium died during the 15 months of the
follow-up, and disease progression was markedly attenuated when
compared with age-, disease duration-, and sex-matched control patients
treated with riluzole for the same amount of time. In a parallel study
on a genetic ALS animal model, the G93A mouse, we found a marked
neuroprotection by lithium, which delayed disease onset and duration
and augmented the life span. These effects were concomitant with
activation of autophagy and an increase in the number of the
mitochondria in motor neurons and suppressed reactive astrogliosis.
Again, lithium reduced the slow necrosis characterized by mitochondrial
vacuolization and increased the number of neurons counted in lamina VII
that were severely affected in saline-treated G93A mice. After lithium
administration in G93A mice, the number of these neurons was higher
even when compared with saline-treated WT. All these mechanisms may
contribute to the effects of lithium, and these results offer a
promising perspective for the treatment of human patients affected by
ALS." http://www.pnas.org/cgi/reprint/105/6/2052
Lithium at 50: have the
neuroprotective effects of this unique cation been overlooked?
Biological Psychiatry. 1999 Oct 1;46(7):929-40. PMID: 10509176 [PubMed]
Manji HK, Moore GJ, Chen G.
Department of Psychiatry and Behavioral Neurosciences,
Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
"Recent advances in cellular and molecular biology have resulted in the
identification of two novel, hitherto completely unexpected targets of
lithium's actions, discoveries that may have a major impact on the
future use of this unique cation in biology and medicine. Chronic
lithium treatment has been demonstrated to markedly increase the levels
of the major neuroprotective protein, bcl-2 in rat frontal cortex,
hippocampus, and striatum. Similar lithium-induced increases in bcl-2
are also observed in cells of human neuronal origin, and are observed
in rat frontal cortex at lithium levels as low as approximately 0.3
mmol/L. Bcl-2 is widely regarded as a major neuroprotective protein,
and genetic strategies that increase bcl-2 levels have demonstrated not
only robust protection of neurons against diverse insults, but have
also demonstrated an increase the regeneration of mammalian CNS axons.
Lithium has also been demonstrated to inhibit glycogen synthase kinase
3 beta (GSK-3 beta), an enzyme known to regulate the levels of
phosphorylated tau and beta-catenin (both of which may play a role in
the neurodegeneration observed in Alzheimer's disease). Consistent with
the increases in bcl-2 levels and inhibition of GSK-3 beta, lithium has
been demonstrated to exert robust protective effects against diverse
insults both in vitro and in vivo. These findings suggest that lithium
may exert some of its long term beneficial effects in the treatment of
mood disorders via underappreciated neuroprotective effects. To date,
lithium remains the only medication demonstrated to markedly increase
bcl-2 levels in several brain areas; in the absence of other adequate
treatments, the potential efficacy of lithium in the long term
treatment of certain neurodegenerative disorders may be warranted."
Rescuing Fruit Flies from Alzheimer's
Disease
ScienceDaily (July 16, 2010)
Investigators have found that fruit fly (Drosophila melanogaster) males
-- in which the activity of an Alzheimer's disease protein is reduced
by 50 percent -- show impairments in learning and memory as they age.
What's more, the researchers were able to prevent the age-related
deficits by treating the flies with drugs such as lithium, or by
genetic manipulations that reduced nerve-cell signaling. The research
team -- Thomas A. Jongens, Ph.D., associate professor of Genetics at
the University of Pennsylvania School of Medicine; Sean M. J. McBride
M.D, Ph.D. and Thomas McDonald M.D., at the Albert Einstein College of
Medicine; and Catherine Choi M.D., Ph.D. at Drexel University College
of Medicine -- worked with the familial form of Alzheimer's disease
(FAD), an aggressive form of the disease that is caused by mutations in
one of the two copies of the presenilin (PS) or amyloid precursor
protein (APP) genes. Studies in animal models have previously shown
that the FAD-linked PS mutations lead to less presenilin (psn) protein
activity. Their findings are published in the Journal of Neuroscience... http://www.sciencedaily.com/releases/2010/07/100715172014.htm
******************************************************************************************** Corticobasal Ganglionic Degeneration (CBD
or CBGD):
Here is a brief description of corticobasal ganglionic degeneration
(CBGD):
from
"Corticobasal degeneration (CBD), also known as corticobasal ganglionic
degeneration (CBGD), was first described in the late 1960’s by Drs.
Rebeiz, Kolodny, and Richardson. Following a lengthy period with no
additional reports, several more patients were identified and their
symptoms and autopsy findings were described in the 1980’s and 1990’s.
Patients typically have symptoms reflecting dysfunction in the cerebral
cortex (thus the term “cortical” or “cortico-”) and basal ganglia (thus
the terms “basal” or “basal ganglionic”), and symptoms are usually worse
on one side of the body. Specifically, cortical dysfunction is
manifested as poor coordination of the arms or legs (apraxia), tendency
for the arm “to act as if it has a mind of its own” (alien limb
phenomenon), numbness or odd sensations (cortical sensory loss), poor
comprehension and/or expression of language (aphasia), and quick jerks
(myoclonus). Slowness of movement (bradykinesia), stiffness in a limb
(rigidity), fixed muscle contractions such as when the fingers curl into
a fist (dystonia), and tremor are presumed to reflect basal ganglia
dysfunction. Some patients develop memory impairment and/or
personality/behavioral changes. Problems with walking eventually occur
in almost all. In our studies the duration of illness from onset of
symptoms to death has ranged from 3-13 years. The vast majority of
patients do not appear to have any family history of dementia or
parkinsonism, although there are rare cases in whom a hereditary process
may be at play. The cause of CBD is not yet known.
"This illness is frustrating to patients, their families, and the
physicians who care for them. Since insight and memory tends to be
preserved throughout most of their illness, depression is common and
should be treated when it evolves. Physical, occupational, and speech
therapy can be helpful although as the illness progresses third party
payers tend to not reimburse for these services, unfortunately.
Medications provide little benefit, but agents such as Sinemet are worth
trying. All sleep disorders such as sleep apnea and restless legs
syndrome should be evaluated and treated as improvement in quality of
life for patients and their loved ones can occur." http://www.tornadodesign.com/cbgd/boeve_updateoncbgd.htm
Corticobasal Degeneration: Evaluation of Cortical Atrophy by Means of
Hemispheric Surface Display Generated with MR Images
"RESULTS: The extent and magnitude of cortical atrophy were larger in
the group with corticobasal degeneration than in the group with
Alzheimer disease. The parasagittal and paracentral regions were
significantly more atrophic in patients with corticobasal degeneration
than in patients with Alzheimer disease (P < .05). The mean
hemispheric-to-total intracranial volume ratios were significantly
smaller in the patients with corticobasal degeneration (61%) and those
with Alzheimer disease (64%) than in control subjects (69%). Asymmetry
of hemispheric volume was significantly larger in the group with
corticobasal degeneration than in the control group.
"CONCLUSION: The extent of cortical atrophy in corticobasal degeneration
is more widespread than was previously thought. Parasagittal and
paracentral atrophy is a distinctive feature of corticobasal
degeneration and distinguishes it from Alzheimer disease."
Corticobasal
Degeneration
Information
for
Patients
and
Caregivers
"Corticobasal degeneration (CBD) is a rare neurological disease in
which parts of the brain deteriorate or degenerate. CBD is also known
as corticobasal ganglionic degeneration, or CBGD...
Several regions of the brain degenerate in CBD. The cortex, or outer
layer of the brain, is severely affected, especially the
fronto-parietal regions, located near the center-top of the head.
Other, deeper brain regions are also affected, including parts of the
basal ganglia, hence the name "corticobasal" degeneration. The combined
loss of brain tissue in all these areas causes the symptoms and
findings seen in people with CBD." http://www.wemove.org/cbd/
NINDS Corticobasal Degeneration
Information Page
"Corticobasal degeneration is a progressive neurological disorder
characterized by nerve cell loss and atrophy (shrinkage) of multiple
areas of the brain including the cerebral cortex and the basal ganglia.
Corticobasal degeneration progresses gradually."
Cortical Basal Ganglionic Degeneration
"Cortical basal ganglionic degeneration (CBGD) may be considered a
syndrome rather than a disease. Its defining clinical characteristics
(ie, progressive dementia, parkinsonism, limb apraxia) may occur as a
result of heterogenous neuropathological conditions such as Pick
complex disorders (see Pick Disease), Alzheimer disease, and even rare
disorders such as CNS Whipple disease and Niemann-Pick type C.
Histopathologically identifiable CBGD can also present clinically as
primary progressive aphasia or primary progressive apraxia in patients
who had no prominent movement disorders earlier in their lives." http://www.emedicine.com/neuro/topic77.htm
Corticobasal Degeneration
"Corticobasal degeneration is a progressive neurological disorder
characterized by nerve cell loss and atrophy (shrinkage) of multiple
areas of the brain including the cerebral cortex and the basal ganglia." http://healthlink.mcw.edu/article/921395030.html
CORTICOBASAL DEGENERATION (CBD)
Corticobasal degeneration, sometimes referred to as corticobasal
ganglionic degeneration (CBGD), is a heterogeneous disease which
clinically, genetically and pathologically is similar to, or overlaps
with frontotemporal dementia (FTD). For this reason, CBD is considered
to be part of the ‘Pick complex’ of neurodegenerative diseases" http://memory.ucsf.edu/Education/Disease/cbd.html
Corticobasal Degeneration
"Corticobasal degeneration (CBD) is a neurodegenerative disease that
was first described by Rebeiz et al., who referred to the disorder as
"corticodentatonigral degeneration with neuronal achromasia." Other
terms for this disease include corticonigral degeneration and
cortical-basal ganglionic degeneration" http://www.treatment-options.com/article.cfm?PubID=NE05-2-2-03&Type=Article&KeyWords=
The Association for Frontotemporal
Dementias Corticobasal Degeneration
Overview
"Corticobasal Degeneration (CBD) is a progressive neurological disorder
that presents primarily as a movement disorder, characterized by lack
of movement and muscle rigidity. Initial symptoms, which typically
begin at or around age 60, may first appear on one side of the body
(unilateral), but eventually affect both sides as the disease
progresses. A patient with CBD may first present with language
disorder, and develop the motor symptoms over time..." http://www.ftd-picks.org/?p=diseases/corticobasaldegeneration
******************************************************************************************** Copper: Scientists Discover Link Between
Alzheimer's And Copper
Medical News Today 07 Nov 2007
"Copper can damage a molecule that escorts out of the brain a substance
called amyloid beta that builds up in toxic quantities in the brains of
people with Alzheimer's disease. The new findings demonstrate one way
in which copper might contribute to the development of the disease,
though scientists say much more research needs to be done to clarify
what role, if any, copper ultimately plays... For decades, many
scientists have hypothesized that a variety of metals, including
aluminum, iron, zinc and copper, might play a role in Alzheimer's
disease, but no link has ever been proven. In the past few years,
several scientists have reported that copper is one component of the
amyloid beta clumps -- tiny trash heaps filled with all sorts of
molecules and substances -- that speckle the brains of people with
Alzheimer's disease... The new results go much further, showing that
copper damages the major known system the brain uses to get rid of
amyloid beta." http://www.medicalnewstoday.com/articles/88024.php
Protective Role For Copper In
Alzheimer’s Disease
ScienceDaily (Oct. 13, 2009)
Two articles in a forthcoming issue of the Journal of Alzheimer’s
Disease -- by Dr Chris Exley, Reader in Bioinorganic Chemistry in the
Research Institute for the Environment, Physical Sciences and Applied
Mathematics at Keele University, UK, and Dr Zhao-Feng Jiang, of Beijing
Union University, Beijing, China -- have confirmed a potentially
protective role for copper in Alzheimer’s disease... A central tenet of
the Amyloid Cascade Hypothesis of Alzheimer’s disease is the aberrant
deposition in the brain of Aβ42 in β-sheets in neuritic or senile
plaques. The Keele team have shown in previous research in JAD that
copper (Cu(II)) prevents the deposition of Aβ42 in β-sheets while in
the current research they show that Cu(II) abolishes the β-sheet
structure of preformed amyloid fibrils of Aβ42. A similar finding was
made by the group of Jiang for the other form of beta amyloid, Aβ40,
and together these observations strongly suggest that copper prevents
both the formation and the accumulation of plaques in the brain... http://www.sciencedaily.com/releases/2009/10/091008133457.htm
Prevention of isoproterenol-induced
tau hyperphosphorylation by melatonin in the rat.
Wang XC, Zhang J, Yu X, Han L, Zhou ZT, Zhang Y, Wang JZ.
Department of Pathophysiology, Tongji Medical College, Huazhong
University of Science and Technology
Sheng Li Xue Bao. 2005 Feb 25;57(1):7-12.
"Hyperphosphorylated microtubule-associated protein tau is the major
protein component of neurofibrillary tangles in the brain of patients
with Alzheimer's disease (AD). Until now, there is no effective cure to
arrest this hyperphosphorylation. The present study was designed to
explore the in vivo preventive effect of melatonin on Alzheimer-like
tau hyperphosphorylation. Isoproterenol, a beta-receptor agonist, was
used to induce tau hyperphosphorylation, and for preventive effect of
melatonin, the rats were injected intraperitoneally with melatonin for
5 d before hippocampi infusion of isoproterenol. The level of tau
phosphorylation was detected by Western blot and immunohistochemistry
using sites specific antibodies (PHF-1 and Tau-1), and it was
normalized by non-phosphorylation dependent total tau antibody (111e).
The results by Western blot showed that the immunoreaction of tau at
PHF-1 epitope was enhanced, and the reaction at Tau-1 epitope was
weakened significantly at 48 h after injection of isoproterenol,
suggesting hyperphosphorylation of tau at Ser 396/Ser 404 (PHF-1) and
Ser199/Ser 202 (Tau-1) sites. Similar results were observed by
immunohistochemistry staining, in which hyperphosphorylated tau was
mainly detected in mossy fibers of hippocampal CA3 region.
Pre-injection of rats with melatonin intraperitoneally arrested
effectively the isoproterenol-induced tau hyperphosphorylation at both
Tau-1 and PHF-1 sites, implying the preventive effect of melatonin in
Alzheimer-like tau hyperphosphorylation."
Vinpocetine benefit and side effects
Vinpocetine is chemically related to, and derived from vincamine, an
alkaloid found in the periwinkle plant. Vinpocetine was
introduced into clinical practice in Europe more than two decades ago
for its role in cerebrovascular disorders and related symptoms.
Experiments with vinpocetine indicate that it can dilate blood vessels,
enhance circulation in the brain, improve oxygen utilization, make red
blood cells more pliable, and inhibit aggregation of platelets.
Vinpocetine even has antioxidant properties. Levels peak in the
bloodstream within an hour and a half after ingestion. Vinpocetine
easily crosses the blood-brain barrier.
http://www.raysahelian.com/vinpocetine.html
Is Vinpocetine the Answer to Brain
Fog, Cognitive and Memory Problems?
Popular European Supplement, Now Available in U.S., Helps Boost Oxygen
in Brain
By Mary Shomon, About.com
About.com
It might be, says Bernd Wollschlaeger, MD, a Florida-based
board-certified family physician who specializes in the application of
herbal remedies and nutritional supplements. Dr. Wollschlaeger is also
the associate editor of the Journal of the American Nutraceutical
Association (JANA).
Vinpocetine (pronounced vin-poe-ce-teen), is a nutritional supplement
derived from the periwinkle plant. It has just recently become
available in the U.S. through food, drug and mass market retailers as a
nutritional supplement. The supplement is already very much in use in
Europe, where physicians believe it is far more effective than other
supplements -- such as ginkgo biloba -- used for memory and brain
function. Vinpocetine actually contains many of the same
cerebral-enhancing effects as ginkgo biloba, but has been shown to be
more effective in much shorter time.
Vinpocetine has been extensively studied in Europe. These clinical
studies have found it to provide several advantages for the human
brain, including memory enhancement, increased cognitive performance,
improved cerebral circulation and higher mental acuity and awareness. http://thyroid.about.com/cs/alternativehelp/a/vinpocetine.htm
Vinpocetine
From Cathy Wong
About.com
Vinpocetine (pronounced vin-poe-ce-teen) is a synthetic compound
derived from vincamine, a substance found naturally in the leaves of
the lesser periwinkle plant (Vinca minor). Vinpocetine was developed in
the late 1960s.
Vinpocetine is available as a prescription drug in Europe and Japan. In
the the United States and Canada, it’s sold in health food stores and
online as a dietary supplement.
Why Do People Use Vinpocetine
Stroke and vascular dementia...
Alzheimer's disease...
Vinpocetine is also being explored as a complementary treatment for
people with Alzheimer’s disease. It’s thought to enhance the brain's
use of oxygen, protect brain cells against damage, and increase blood
flow to the brain by inhibiting an enzyme called phosphodiesterase.
Although preliminary studies on the use of vinpocetine for Alzheimer's
disease showed promise, a critical review of previously published
studies found that the evidence as a whole was too weak to rely on, due
to limitations in the design of the studies. More research is needed.
Vinpocetine by Douglas Labs
"VinpocetineVinpocetine is an extract of the periwinkle plant. Its
discovery has essentially revolutionized the treatment of vascular
dementia. It is a cognitive enhancer that has been demonstrated to
increase brain blood flow, increase brain metabolism and act as a
potent antioxidant." http://www.jonnybowden.com/products/product_vinpocetine.html
Vinpocetine for cognitive impairment
and dementia
by Szatmari Sz, Whitehouse PJ
The Cochrane Collaboration, Cochrane Reviews
"Insufficient evidence of benefits of vinpocetine for people with
dementia. Preclinical data of uneven quality suggest a potential
beneficial effect of vinpocetine in chronic cerebrovascular diseases
and on cognitive performance in a variety of animal models. Clinical
trials to test these hypotheses were performed before currently used
criteria for dementia had become generally accepted. The results show
improvement after the treatment with vinpocetine versus placebo, but
the number of demented patients treated for at least six months was
small. The available data does not demonstrate many side effect
problems. Although the basic science is interesting, the evidence for
beneficial effect of vinpocetine on patients with dementia is
inconclusive and does not support clinical use." http://www.cochrane.org/reviews/en/ab003119.html
Vinpocetine
From Wikipedia
"Vinpocetine (brand names: Cavinton, Intelectol; chemical name: ethyl
apovincaminate) is a semisynthetic derivative alkaloid of vincamine
(sometimes described as "a synthetic ethyl ester of apovincamine"), an
extract from the periwinkle (plant) Vinca minor. Vinpocetine is
reported to have cerebral blood-flow enhancing and neuroprotective
effects, and is used as a drug in Eastern Europe for the treatment of
cerebrovascular disorders and age-related memory impairment.
Vinpocetine is widely marketed as a supplement for vasodilation and as
a nootropic for the improvement of memory. There exists anecdotal
report of uncomfortable adverse reactions to vinpocetine in a small
subset of users. A low initial dosage is often recommended..." http://en.wikipedia.org/wiki/Vinpocetine
Vinpocetine
PDRhealth
"What is it? Vinpocetine is an herbal supplement used to treat
thinking and memory problems, such as Alzheimer's disease. Other
names for Vinpocetine include: Ethyl apovincaminate, Ethyl
apovincaminoate, and vinca minor. Ask your doctor, nurse, or
pharmacist if you need more information about this medicine or if any
information in this leaflet concerns you..." http://www.pdrhealth.com/drugs/altmed/altmed-mono.aspx?contentFileName=ame0376.xml&contentName=Vinpocetine&contentId=532
Vinpocetine
ThirdAge
Vinpocetine is a chemical derived from vincamine, a constituent found
in the leaves of common periwinkle ( Vinca minor L.) as well as the
seeds of various African plants. It is used as a treatment for memory
loss and mental impairment.
Developed in Hungary over 20 years ago, vinpocetine is sold in Europe
as a drug under the name Cavinton. In the United States it is available
as a "dietary supplement," although the substance probably doesn't fit
that category by any rational definition. Vinpocetine doesn't exist to
any significant extent in nature. Producing it requires significant
chemical work performed in the laboratory.
What Is Vinpocetine Used for Today?
Some evidence supports the idea that vinpocetine can enhance memory and
mental function, especially in those with Alzheimer's disease and
related conditions. It is also widely marketed for enhancing memory in
healthy people, but there is no real evidence that it is helpful for
this purpose.
It has been hypothesized that vinpocetine helps people with Alzheimer’s
disease by enhancing blood flow in the brain, safeguarding brain cells
against damage, and inhibiting a substance known as phosphodiesterase.
1–3
Based on these proposed actions, vinpocetine has also been tried as a
treatment for reducing brain damage following strokes .
What Is the Scientific Evidence for Vinpocetine?
Alzheimer’s Disease and Related Condtions (Dementia)
A 16-week, double-blind, placebo-controlled trial of 203 individuals
with mild to moderate dementia found significant benefit in the treated
group. 4 Benefits have been seen in other studies as well. 5–10
However, a major review found that overall the evidence that it works
remains too weak to rely upon, due to limitations in study quality. 19
Strokes
In a single-blind , placebo-controlled trial, 30 individuals who had
just experienced a stroke received either placebo or vinpocetine along
with conventional treatment for 30 days. 11 The results showed that
participants in the vinpocetine group experienced a significantly
reduced level of residual disability as measured at 3 months.
A few other studies, some of poor design, also provide suggestive
evidence that vinpocetine may be helpful for strokes. 12,16,17,20
However, much of the existing evidence is too preliminary to rely on,18
and a recent review combining two relatively high quality studies
involving 63 subjects was unable to determine whether or not
vinpocetine provided any benefit for stroke patients.21
Note: People who have had strokes are sometimes advised to take blood
thinning drugs. There are concerns that vinpocetine may interact
adversely with some medications of this type. See Safety Issues below.
Dosage
The usual dose of vinpocetine is 10-mg capsules 3 times per day,
although dosages ranging from half to twice that amount have been used
in studies. Vinpocetine reportedly is better absorbed when taken with a
meal. 13
Safety Issues
No serious side effects have been reported in any of the clinical
trials. However, there is one case report of vinpocetine apparently
causing agranulocytosis (loss of certain white blood cells). 15
Vinpocetine inhibits blood platelets from forming clots, 1 and for this
reason it couldcause problems if it is taken by individuals with
bleeding problems, during the period immediately before or after
surgery or labor and delivery, or in combinationwith medications or
natural substances that also affect platelet activity, such as aspirin
, clopidogrel (Plavix), ticlopidine (Ticlid), pentoxifylline (Trental),
garlic , ginkgo , policosanol , or high-dosage vitamin E .
The drug warfarin (Coumadin) affects blood clotting, but not through
actions on platelets. One study found only a minimal interaction
between warfarin and vinpocetine, and interestingly, it was in the
direction of decreased clotting. 14 Nonetheless, combination therapy
with vinpocetine and warfarin should not be attempted except under the
supervision of a physician.
Safety in pregnant or nursing women, young children, or those with
severe liver or kidney disease has not been established.
Interactions You Should Know About
* Simultaneous use of vinpocetine with
blood-thinning drugs, such as aspirin , clopidogrel (Plavix),
ticlopidine (Ticlid), or pentoxifylline (Trental), might cause bleeding
problems.
* It is also possible that simultaneous use of
vinpocetine in combination with natural substances with blood-thinning
properties, such as garlic , ginkgo , policosanol , or high-dose
vitamin E , might cause bleeding problems.
* Vinpocetine might impair the action of the blood
thinning drug warfarin (Coumadin)
References
1. Kiss B, Karpati E. Mechanism of action of vinpocetine
[in Hungarian; English abstract]. Acta Pharm Hung . 1996;66:213–214.
2. Miyazaki M. The effect of a cerebral vasodilator,
vinpocetine, on cerebral vascular resistance evaluated by the Doppler
ultrasonic technique in patients with cerebrovascular diseases.
Angiology. 1995;46:53–58.
3. Bereczki D, Fekete I. A systematic review of vinpocetine
therapy in acute ischaemic stroke. Eur J Clin Pharmacol.
1999;55:349–352.
4. Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and
tolerance of vinpocetine in ambulant patients suffering from mild to
moderate organic psychosyndromes. Int Clin Psychopharmacol .
1991;6:31–43.
5. Balestreri R, Fontana L, Astengo F. A double-blind
placebo controlled evaluation of the safety and efficacy of vinpocetine
in the treatment of patients with chronic vascular senile cerebral
dysfunction. J Am Geriatr Soc . 1987;35:425–430.
6. Dragunow M, Faull RL. Neuroprotective effects of
adenosine. Trends Pharmacol Sci . 1988;9:193–194.
7. Fenzl E, Apecechea M, Schaltenbrand R, et al. Efficacy
and tolerance of vinpocetine administered intravenously, in addition of
standard therapy, to patients suffering from an apoplectic insult. In:
Krieglstein J, ed. Pharmacology of Cerebral Ischemia: Proceedings of
the International Symposium on Pharmacology of Cerebral Ischemia. New
York, NY: Elsevier Science Publishers; 1986:430–434.
8. Manconi E, Binaghi F, Pitzus F. A double-blind clinical
trial of vinpocetine in the treatment of cerebral insufficiency of
vascular and degenrative origin. Curr Ther Res Clin Exp .
1986;30:702–709. Cited by: Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy
and tolerance of vinpocetine in ambulant patients suffering from mild
to moderate organic psychosyndromes. Int Clin Psychopharmacol .
1991;6:31–43.
9. Peruzza M, DeJacobis M. A double-blind placebo
controlled evaluation of the efficacy and safety of vinpocetine in the
treatment of patients with chronic vascular or degenerative senile
cerebral dysfunction. Adv Ther .1986;3:201–209. Cited by: Hindmarch I,
Fuchs HH, Erzigkeit H. Efficacy and tolerance of vinpocetine in
ambulant patients suffering from mild to moderate organic
psychosyndromes. Int Clin Psychopharmacol . 1991;6:31–43.
10. Blaha L, Erzigkeit H, Adamczyk A, et al. Clinical
evidence of the effectiveness of vinpocetine in the treatment of
organic psychosyndrome. Hum Psychopharmacol. 1989;4:103–111. Cited by:
Hindmarch I, Fuchs HH, Erzigkeit H. Efficacy and tolerance of
vinpocetine in ambulant patients suffering from mild to moderate
organic psychosyndromes. Int Clin Psychopharmacol . 1991;6:31–43.
11. Feigin VL, Doronin BM, Popova TF, et al. Vinpocetine
treatment in acute ischaemic stroke: a pilot single-blind randomized
clinical trial. Eur J Neurol. 2001;8:81–85.
12. Bereczki D, Fekete I. A systematic review of
vinpocetine therapy in acute ischaemic stroke. Eur J Clin Pharmacol.
1999;55:349–352.
13. Lohmann A, Dingler E, Sommer W, et al. Bioavailability
of vinpocetine and interference of the time of application with food
intake. Arzneimittelforschung . 1992;42:914–917.
14. Hitzenberger G, Sommer W, Grandt R. Influence of
vinpocetine on warfarin-induced inhibition of coagulation. Int J Clin
Pharmacol Ther Toxicol . 1990;28:323–328.
15. Shimizu Y, Saitoh K, Nakayama M, et al. Agranulocytosis
induced by vinpocetine. Medicine Online [serial online]. Available at:
http://www.priory.com/med/vinpocetine.htm . Accessed July 20, 2002.
16. Feigin VL, Doronin BM, Popova TF, Gribatcheva EV,
Tchervov DV. Vinpocetine treatment in acute ischaemic stroke: a pilot
single-blind randomized clinical trial. Eur J Neurol. 2001;8(1):81-85.
17. Bonoczk P, Panczel G, Nagy Z. Vinpocetine increases
cerebral blood flow and oxygenation in stroke patients: a near infrared
spectroscopy and transcranial Doppler study. Eur J Ultrasound.
2002;15(1-2):85-91.
18. Bereczki D, Fekete I. Vinpocetine for acute ischaemic
stroke (Cochrane Review). In The Cochrane Library , Issue 2, 2000.
Oxford, England: Update Software. Updated quarterly.
19. Szatmari SZ, Whitehouse PJ. Vinpocetine for cognitive
impairment and dementia. Cochrane Database Syst Rev . 2003;(1):CD003119
20. Szilagyi G, Nagy Z, Balkay L et al. Effects of
vinpocetine on the redistribution of cerebral blood flow and glucose
metabolism in chronic ischemic stroke patients: a PET study. J Neurol
Sci . 2005;229-230:275-84.
Lack of Efficacy of Vinpocetine in
Vascular Dementia
by B. Robertsson, A. Wallin, A.L. Nyth, C.G. Gottfries, K. Blennow
Department of Psychiatry and Neurochemistry, University of
Göteborg, Sweden
Dementia 1990;1:316-322 (DOI: 10.1159/000107159)
Abstract:
Twenty-two patients suffering from mild to moderate dementia of
vascular origin were treated with vinpocetine, 30 mg/day during 16
weeks, in an open pilot study. Response to treatment was assessed with
the Gottfries-Bråne-Steen geriatric rating scale and psychometric
tests. Effects on concentrations of neurotransmitters in the
cerebrospinal fluid (CSF) and on the blood-brain barrier function were
also studied. According to the ratings and tests, the only noticeable
improvement was reduced fear/panic. This improvement may very well be
attributable to increased care of the patients during the study. The
drug did not influence the monoamine metabolites in the CSF or the
blood-brain barrier function. On the basis of these results we conclude
that vinpocetine has no effect on patients suffering from mild to
moderate dementia of vascular origin. http://content.karger.com/ProdukteDB/produkte.asp?Doi=107159
Oh... and this rather interesting article from "Neurology India" was in
that folder. Not really realted to vinpocetine, but it is
interesting. Note the very low incidence of AD in India. Is
it genetic or diet? Curcumin has been shown to have anti-amyloid
and anti-inflammatory properties and is an iron and copper
chelator. It is abundant in the cury spice tumeric. Coconut
products are also used in India cusine, I think (MCT oils?)...
Some observations on the spectrum of
dementia
Abstract:
A study was designed to generate epidemiological and clinical data on
dementia, in a teaching hospital in India. It was conducted on 124 (94
male and 30 female) elderly patients (aged more than 60 years)
presenting with clinical syndrome of dementia (DSM-3). Their age range
was 64-78 (mean 65.7 4.1) years. Detailed clinical, biochemical,
radiological and electrophysiological evaluation was done to establish
etiology. Patients with psychiatric ailments, cranial trauma and tumors
were excluded. The study period was 4.2 years. Multi-infarct dementia
(MID) was observed to be commonest cause of dementia and was present in
59 (47.6%) cases. There were 10 (8%) patients each of tuberculosis (TB)
and neurocysticercosis (NCC). Alcohol-related dementia was present in
13 (10.5%), while malnutrition (Vitamin B12 deficiency) was present in
9 (7.2%). Alzheimer's Disease (AD) was present (NINCDS-ADRDA criteria)
in 6 patients (4.8%). There were 3 (2.4%) cases 1 each of Huntington's
disease, Parkinson's and Normal Pressure Hydrocephalus and 2 each of
diabetes, hypothyroidism, hyperthyroidism and Creutzfeldt' Jakob
Disease. We conclude that AD, which is irreversible and common in the
west, is relatively uncommon in India as compared to MID, infections
and malnutrition, which are potentially treatable. http://www.neurologyindia.com/article.asp?issn=0028-3886;year=2004;volume=52;issue=2;spage=213;epage=214;aulast=Jha
"Researchers at the University of California, Santa Barbara have
discovered an extract of common cinnamon that contains a class of small
organic molecules that inhibit several key processes in Alzheimer's
disease.
The cinnamon extract inhibits the aggregation of tau and disassembles
fibers that have already formed, suggesting that neurofibrillary
tangles can possibly be reversed by these compounds.
The extract exhibits potent inhibitory activity, is orally available,
water-soluble, non-toxic, and the bioactive molecules are likely brain
permeable. The extract is readily produced in large quantities and can
be encapsulated in powder form for oral administration. These
properties make the cinnamon extract a highly favorable substance for
development into an effective therapeutic to slow or prevent
Alzheimer's disease." http://www.ibridgenetwork.org/innovations/download_tech_brief/3417
PROANTHOCYANIDINS
FROM
CINNAMON
AND
ITS
WATER
SOLUBLE EXTRACT
INHIBIT TAU AGGREGATION
Abstract: Compositions
comprising proanthocyanidin compositions (e.g.
those extracted from cinnamomum species) that are observed to bind tau
and inhibit its aggregation as well as methods for making and using such compositions are
disclosed. In certain embodiments of the
invention, the proanthocyanidins can be used as a probe to identify
and/or characterize tau isoforms in a variety of contexts. In other
embodiments of the invention, these compositions are used in methods
designed to treat neurological disorders associated with tau
aggregation (e.g. Alzheimer's disease).
Pub. No.: WO/2008/121412
International Application No.:
PCT/US2008/004236 Publication Date: 09.10.2008
International Filing Date: 31.03.2008
IPC: A61K 36/54 (2006.01) Applicants: THE REGENTS OF THE
UNIVERSITY OF CALIFORNIA [US/US]; 1111 Franklin Street, 12th Floor,
Oakland, CA 94607 (US) (All Except US). LEW, John [CA/US]; (US) (US
Only). GRAVES, Donald, J. [US/US];
(US) (US Only). Inventors: LEW, John; (US). GRAVES, Donald, J.; (US). http://www.wipo.int/pctdb/en/wo.jsp?WO=2008121412 http://www.wipo.int/pctdb/en/wo.jsp?WO=2008121412&IA=US2008004236&DISPLAY=DESC Cinnamon Extract Inhibits Tau
Aggregation Associated with Alzheimer's Disease In Vitro Journal Journal of Alzheimer's Disease Publisher IOS Press ISSN 1387-2877 (Print)
1875-8908 (Online) Issue Volume 17, Number 3 / 2009 DOI 10.3233/JAD-2009-1083 Pages 585-597 Subject Group Neurosciences Authors Dylan W. Peterson1,
Roshni C. George1, Francesca
Scaramozzino1, Nichole E. LaPointe1, Richard A.
Anderson2, Donald J. Graves1, John Lew1 1Department of
Molecular, Cellular, and Developmental
Biology, University of California, Santa Barbara, CA, USA 2Beltsville Human
Nutrition Center, Beltsville, MD, USA
Abstract An aqueous extract of Ceylon
cinnamon (C. zeylanicum) is found to
inhibit tau aggregation and filament formation, hallmarks of
Alzheimer's disease (AD). The extract can also promote complete
disassembly of recombinant tau filaments and cause substantial
alteration of the morphology of paired-helical filaments isolated from
AD brain. Cinnamon extract (CE) was not deleterious to the normal
cellular function of tau, namely the assembly of free tubulin into
microtubules. An A-linked proanthocyanidin trimer molecule was purified
from the extract and shown to contain a significant proportion of the
inhibitory activity. Treatment with polyvinylpyrolidone effectively
depleted all proanthocyanidins from the extract solution and removed
the majority, but not all, of the inhibitory activity. The remainder
inhibitory activity could be attributed to cinnamaldehyde. This work
shows that compounds endogenous to cinnamon may be beneficial to AD
themselves or may guide the discovery of other potential therapeutics
if their mechanisms of action can be discerned. http://iospress.metapress.com/content/06h5g61751404678/ http://www.ncbi.nlm.nih.gov/pubmed/19433898?dopt=Abstract
Research Project: CHROMIUM AND POLYPHENOLS FROM CINNAMON IN
THE PREVENTION AND ALLEVIATION OF GLUCOSE INTOLERANCE
Location: Diet, Genomics and Immunology Lab
Title: Polyphenols, Insulin Sensitivity, and the Brain
Authors
item Anderson, Richard
item Panickar, Kiran
Submitted to: Meeting Abstract
Publication Type: Abstract
Publication Acceptance Date: June 1, 2009
Publication Date: N/A
Technical Abstract: We
have isolated water-soluble polyphenols found in cinnamon that are
multifunctional and improve insulin sensitivity, glucose uptake, and
have antioxidant and anti-inflammatory properties in experimental
animals and humans. These compounds may also be potentially
neuroprotective as oxidative stress, abnormalities in glucose
utilization, and inflammation, are also all implicated in neurological
disorders. Abnormalities in insulin signaling in the brain can
contribute to Alzheimer¿s disease (AD) and AD has recently been
called ¿type 3 diabetes¿ due to the observation that
abnormalities in insulin signaling in the brain associated with AD are
similar to those observed in insulin sensitive tissues of people with
type 2 diabetes. Neuropathologically, AD is characterized by the
deposition of extracellular plaques, composed principally of amyloid
ß protein, and intracellularly of neurofibrillary tangles,
generally associated with hyperphosphorylated tau. Polyphenols from
cinnamon inhibit both tau aggregation and amyloid ß filament
formation. Oxidative stress and mitochondrial dysfunction are key
events implicated in both neuronal and astrocytic dysfunction/death and
cinnamon and tea polyphenols, as well as insulin, protect neuronal
death in cultures from Aß toxicity. Mitochondrial dysfunction in
neurons from Aß toxicity is also protected by these polyphenols.
Ischemic stroke is caused by an interruption of cerebral blood flow,
which can lead to vascular leakage, inflammation, tissue injury, and
necrosis. Polyphenols from cinnamon and tea have neuroprotective
effects in PC12 neuronal cells subjected to oxygen-glucose deprivation.
One neuroprotective mechanism of such polyphenols may be due to their
effects on improving mitochondrial membrane potential/mitochondrial
function. Glial swelling, a key feature of cytotoxic edema, due to
oxygen-glucose deprivation, is also prevented by cinnamon and tea
polyphenols in C6 glial cells. In addition, green tea
epigallocatechin-3-gallate improves insulin sensitivity, reduces
beta-amyloid levels and plaques and delays memory regression in mice.
In summary, in vitro studies demonstrate that cinnamon and tea
polyphenols not only improve insulin sensitivity but also protect
neuronal and glial cells from ischemic injury and amyloid ß
toxicity. Animal studies demonstrate that tea polyphenols reverse or
alleviate signs and symptoms of Alzheimer¿s disease and
premature losses in memory regression. Human studies demonstrate that
increased intake of cinnamon and tea polyphenols leads to improved
insulin sensitivity and related pathologies associated with aging.
Project Team
Anderson, Richard
Urban, Joseph
Schoene, Norberta http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=229553
Tumor Necrosis Factor-alpha
Stimulates the Overproduction of Intestinal Apolipoprotein
B48-containing Very Low Density Lipoproproteins
Authors
item Qin, Bolin - ARS RESEARCH ASSOCIATE
item Khosrowl, Adeli - UNIV OF TORONTO, ONTARIO
item Anderson, Richard
Research conducted cooperatively with:
item Integrity Nutraceuticals International
Submitted to: Diabetes
Publication Type: Abstract
Publication Acceptance Date: March 12, 2008
Publication Date: June 10, 2008
Citation: Qin, B., Khosrowl, A., Anderson, R.A. 2008. Tumor Necrosis
Factor-alpha Stimulates the Overproduction of Intestinal Apolipoprotein
B48-containing Very Low Density Lipoproproteins. Diabetes. 888:102.
Technical Abstract: Tumor necrosis factor-alpha(a)(TNFa), a
proinflammatory cytokine, is involved in obesity-associated pathologies
including type 2 diabetes and atherosclerosis. TNFa enhanced
postprandial apoB48-VLDL1 overproduction by about 89% compared with the
control after 90 min olive oil loading; TNFa did not significantly
affect apoB-48 VLDL2 expression. In addition, acute oral treatment of
Cinnulin PF (a water soluble cinnamon extract, 50 mg per kg BW), which
has insulin-like metabolic actions, inhibits TNFa-induced postprandial
overproduction of apoB48-containing lipoproteins. Fresh isolated
primary enterocytes of hamsters were stimulated with TNFa (10 ng per mL
for 4hs), to investigate the expression of insulin signaling pathway
genes, insulin receptor (IR), IRS1, IRS2, Akt1, and
phosphatidylinositol3-kinase (PI3K), and the key regulators of lipid
metabolism, microsomal triglyceride transfer protein(MTP), sterol
regulatory element-binding protein (SREBP)1c, and phosphatase and
tensin homology (PTEN), as well as the inflammatory factor genes, ILa,
ILBeta, IL6, and TNFa. Quantitative real-time PCR assays showed that
TNFa decreased IR, IRS1, IRS2, PI3K and Akt1 mRNA levels of enterocytes
by 45, 59, 60, 59, and 38%, respectively, of controls. In summary, TNFa
stimulates the postprandial apoB-48 VLDL1 overproduction via regulation
of mRNA levels of proteins in the intestinal insulin signaling pathway,
and perturbs the expression of MTP, PTEN, and SREBP1c, as well as
enhances the expression of inflammation factors. Taken together with
previous studies, the improvement of insulin sensitivity will inhibit
the overproduction of apoB48-containing lipoproteins induced by factors
and diets that increase TNFa levels. http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=222820
******************************************************************************************** Infection and
Immune System Response:
The Emerging Role Of Infection In
Alzheimer's Disease
ScienceDaily (May 25, 2008) — A number of chronic diseases are in fact
caused by one or more infectious agents. For example, stomach ulcers
are caused by Helicobacter pylori, chronic lung disease in newborns and
chronic asthma in adults are both caused by Mycoplasmas and Chlamydia
pneumonia, while some other pathogens have been associated with
atherosclerosis. The realization that pathogens can produce slowly
progressive chronic diseases has opened new lines of research into
Alzheimer's disease. http://www.sciencedaily.com/releases/2008/05/080522155752.htm
Tooth Loss, Dementia May Be Linked,
Study Suggests
ScienceDaily (Oct. 11, 2007) — Tooth loss may predict the development
of dementia late in life, according to research published in the
October issue of The Journal of the American Dental Association. http://www.sciencedaily.com/releases/2007/10/071010111807.htm
Yahoo Group: Dental Cleanse
"Dental Cleanup- removing one of the main causes of "incurable
diseases" and curing "incurable" diseases. Amalgam, Root Canals,
Cavitations Surgery (Curettment), Nickel / Gold Crowns, fluoride,
dental risk. We are people sharing information on health hazard of
Amalgam dental fillings,mercury, Root canal fillings, Gold and Nickel
crowns, and other dental metal. We have been learning from:-Dr.Hulda
Clark, Dr.Hall Higgins, Veston Price, Tom Warren and many other. "What
is it about the mouth that makes this hazardous waste non-toxic?" -
Sandra Denton, M.D. Dentists have the highest suicide and divorce rates
among professional. Female dental personnel have a higher spontaneous
abortion rate, a raised incidence of premature labour, and an elevated
perinatal mortality. - --Research has demonstrated that 100% of all
root canals result in residual infection due to the imperfect seal that
allows bacteria to penetrate. The toxins given off by these bacteria
are more toxic than mercury. These toxins can cause systemic diseases
of the heart, kidney, uterus, and nervous and endocrine systems. --This
list is for healthy people and for people suffering of degenerative
diseases: Cancer,Leukemia,Colitis/Colitus,ALZHEIMER,MS,Irritable Bowel
Syndrom,Chron's disease, Diverticolitis, Ulcerative
Colitis,Constipation, Parasite Infections, Aids, Allergies, Asthma,
Food intollerance, mercury - nickel-thalium - heavy metal poisoning ...
" http://health.groups.yahoo.com/group/dentalcleanse/?yguid=27108277
Profiling the culprit in Alzheimer's
disease (AD): bacterial toxic proteins - Will they be significant for
the aetio-pathogenesis of AD and the transmissible spongiform
encephalopathies?
Schmitt HP.
Institute of Pathology, Department for Neuropathology, University of
Heidelberg, Germany.
Med Hypotheses. 2007;69(3):596-609. Epub 2007 Mar 6.
The aetiology of Alzheimer's disease (AD) and the transmissible
spongiform encephalopathies (tSEs) is still elusive. The concept that
prion protein (PrP(Sc)) is the aetiological agent (infectious protein)
in the tSEs has recently been questioned. In AD, the cause of the
aberrant cleavage of the beta-amyloid precursor protein (APP),
resulting in the production of amyloidogenic Abeta fragments, has yet
remained obscure. Moreover, the amyloid hypothesis of AD has been
seriously challenged. In both AD and the tSEs, pathogens of various
nature, including bacteria, have been discussed as possible causal
factors. However, aetiological considerations have completely neglected
microbial products such as the bacterial toxic proteins (BTPs). The
present paper is aimed at drawing a "culprit profile" of these toxic
molecules that can exert, at low-dosage, neuro-degeneration through
various effects. Clearly, BTPs may affect cell-surface receptors
including modulatory amine transmitter receptor expression, block
neuro-transmitter release, increase intra-cellular Ca(2+) levels,
affect intra-cellular signal transduction, change cyto-skeletal
processing, alter synaptic transmission, influence APP proteolysis,
interact with cell surface proteins like PrP(C) or their GPI anchors,
act as chaperones inducing conformational change in proteins (e.g.,
PrP(C) to PrP(Sc)), alter lipid membrane integrity by affecting
phospholipases or forming pores and channels, induce vacuolar
(spongiform) change and elicit inflammatory reactions with cytokine
production including cytokines that were demonstrated in the AD brain.
Like PrP(Sc), BTPs can be heat-stable and acid-resistant. BTPs can meet
the key-proteins of AD and tSEs in the lipid-rich domains of the plasma
membrane called rafts. Basically, this might enable them to initiate a
large variety of unfavourable molecular events, eventually resulting in
pathogenetic cascades as in AD and the tSEs. All in all, their profile
lends support to the hypothesis that BTPs might represent relevant
culprits capable to cue and/or promote neuro-degeneration in both AD
and the tSEs.
PMID: 17337124 http://www.ncbi.nlm.nih.gov/pubmed/17337124?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
COULD THE ROLE OF PRIONS EXTEND TO
ALZHEIMER'S DISEASE—AND BEYOND?
Jean McCann
NeurologyReviews.com December 1999
Prions—proteinaceous infectious particles that lack nucleic acid—are
most familiar as the pathogenic agents in Creutzfeld-Jakob disease in
humans and scrapie in sheep. However, Dr. Prusiner suggested that they
may also play a role in more common neurodegenerative diseases,
including Alzheimer's disease, Parkinson's disease, amyotrophic lateral
sclerosis, and frontotemporal dementia. If the new compounds prove
successful in treating Creutzfeld-Jakob disease and related conditions,
they may provide a blueprint for intervention in these other diseases
as well. http://www.neurologyreviews.com/dec99/nr_dec99_Prions.html
Eradication of Helicobacter pylori
may be beneficial in the management of Alzheimer’s disease
Journal of Neurology Volume 256, Number 5 / May, 2009
"...At the 2-year clinical endpoint, cognitive and functional status
parameters improved in the subgroup of patients where Hp eradication
was successful..."
Abstract Infectious agents have been proposed as potential causes
of Alzheimer’s disease (AD). Recently, we documented a high prevalence
of Helicobacter pylori (Hp) infection in patients with AD. We aim to
access the effect of Hp eradication on the AD cognitive (MMSE: Mini
Mental State Examination and CAMCOG: Cambridge Cognitive Examination
for the Elderly) and functional (FRSSD: Functional Rating Scale for
Symptoms of Dementia) status parameters. In the first part of the
study, a total of 50 consecutive patients with AD and 30 age-matched
anaemic controls underwent an upper gastrointestinal endoscopy, and
gastric mucosal biopsies were obtained to detect the presence of Hp
infection by histologic analysis and rapid urease test. Serum
anti-Hp-specific IgG level was analysed by enzyme-linked immunosorbent
assay. In the second part, Hp-positive AD patients received a triple
eradication regimen (omeprazole, clarithromycin and amoxicillin), and
all patients were followed up for 2 years, while under the same
treatment with cholinesterase inhibitors. Hp was detected in 88% of AD
patients and in 46.7% of controls (P < 0.001). Hp eradication was
successful in 84.8% of treated patients. At the 2-year clinical
endpoint, cognitive and functional status parameters improved in the
subgroup of patients where Hp eradication was successful (P < 0.001
and P = 0.049 for MMSE and CAMCOG, respectively; P < 0.001 for
FRSSD), but not in the other patients. Hp eradication may positively
influence AD manifestations, suggesting a possible common link between
Hp and AD. http://www.springerlink.com/content/83147756538x7031/?p=4d07d65b60894df3bab4620921dcd1e6&pi=2 http://www.springerlink.com/content/83147756538x7031/fulltext.pdf
Infections May Lead To Faster Memory
Loss In Alzheimer's Disease
ScienceDaily (Sep. 8, 2009)
Getting a cold, stomach bug or other infection may lead to increased
memory loss in people with Alzheimer's disease, according to research
published in the September 8, 2009, print issue of Neurology®, the
medical journal of the American Academy of Neurology.
The study found that people who had respiratory, gastrointestinal or
other infections or even bumps and bruises from a fall were more likely
to have high blood levels of tumor necrosis factor-α, a protein
involved in the inflammatory process, and were also more likely to
experience memory loss or other types of cognitive decline than people
who did not have infections and who had low levels of the protein... http://www.sciencedaily.com/releases/2009/09/090907162306.htm
Broccoli Sprouts Good for the Gut
Compound in Broccoli Sprouts May Protect Against Ulcers, Stomach Cancer
By Jennifer Warner
WebMD Health April 6, 2009
April 6, 2009 -- Munching on broccoli sprouts may help protect the
stomach from the germ responsible for many cases of gastritis, ulcers,
and stomach cancer.
A new study shows that eating 2 1/2 ounces of three-day-old broccoli
sprouts every day for at least two months may offer at least some
protection against the bacterium Helicobacter pylori (H. pylori), one
of the most common bacterial infections in the world.
Researchers say it’s the first study to show a beneficial effect of
broccoli sprouts on a bacterial infection behind stomach cancer.
Broccoli sprouts are much higher than mature broccoli heads in
delivering a biochemical called sulforaphane, which has previously been
shown to have potentially anticancer effects. The compound appears to
work by triggering the body, especially the gastrointestinal tract, to
produce enzymes that protect against damage-causing chemicals and
inflammation...
Better than
Antibiotics in H. Pylori Battle: Broccoli Sprouts Broccoli Sprouts Help Maintain
Optimal Balance of H. Pylori
Jed W. Fahey, ScD
Johns Hopkins School of Medicine and Center for Human Nutrition
Special from Bottom Line's Daily Health News
August 3, 2009
Helicobacter pylori (H. pylori) bacteria presents a medical conundrum
-- while the gut bacteria has been implicated in ulcers and stomach
cancer, it also seems to confer protection against other health
problems, including esophageal cancer. What’s a person to do? One
helpful strategy might be to eat broccoli sprouts. It seems they are a
natural way to help maintain H. pylori at a level that is helpful, not
harmful.
Sitting right next to the much more popular alfalfa sprouts in
groceries and health-food stores, these "baby broccoli plants" are even
better for you than in their grown-up form. New research from Tokyo
University of Science and Johns Hopkins University School of Medicine
investigated how regular consumption of broccoli sprouts affected
people with H. pylori infection, the frequent cause of peptic ulcers
and stomach cancer. The study included 48 H. pylori-infected adults who
were randomly assigned to consume 70 grams a day (about two and
one-half ounces) of either broccoli sprouts or alfalfa sprouts.
Researchers found that after eating broccoli sprouts for eight weeks,
participants significantly lowered biomarkers for H. pylori while those
who ate alfalfa sprouts did not show this benefit.
Jed W. Fahey, ScD, a faculty research associate in the department of
pharmacology and molecular sciences, was a study coauthor. He told me
that the active component against the bacterium is a phytochemical
called sulforaphane. This natural substance induces and boosts some of
the body’s protective anti-inflammatory enzymes and also has antibiotic
properties particularly effective against some strains of H. pylori.
Broccoli sprouts are a much more potent source of sulforaphane than is
even the freshest broccoli, Dr. Fahey said.
A dietary source to combat H. pylori is excellent news for many people.
Estimates are that as many as 50% of Americans harbor the bacteria,
though they don’t always have symptoms. However, when the H. pylori
runs rampant and causes infection, treatment can be tough -- typically
it involves taking two different antibiotics simultaneously, often in
addition to a bismuth preparation or an acid-suppressing protein-pump
inhibitor. The end result of all this is, quite often, yet another
ulcer -- and, in about 20% of patients, it doesn’t even solve the
problem.
Broccoli sprouts offer a natural alternative and an easy and tasty way
to combat H. pylori. Note, however, that the protective effect fades if
you stop eating the sprouts, so you should eat broccoli sprouts
regularly (two to three times a week). Dr. Fahey points out that they
keep for several days in the refrigerator and are wonderful in salads,
sandwiches and wraps.
******************************************************************************************** Methylene
Blue: Potential
Alzheimer's, Parkinson's Cure Found In Century-old Drug
ScienceDaily (Aug. 18, 2008)
"A new study conducted by researchers at Children's Hospital &
Research Center Oakland shows that a century-old drug, methylene blue,
may be able to slow or even cure Alzheimer's and Parkinson's disease.
Used at a very low concentration – about the equivalent of a few
raindrops in four Olympic-sized swimming pools of water – the drug
slows cellular aging and enhances mitochondrial function, potentially
allowing those with the diseases to live longer, healthier lives."
"Methylene blue, first discovered in 1891, is now used to treat
methemoglobinemia, a blood disorder. But because high concentrations of
methylene blue were known to damage the brain, no one thought to
experiment with low concentrations. Also, drugs such as methylene blue
do not easily reach the brain." http://www.sciencedaily.com/releases/2008/08/080818101335.htm
No mention in the full article of its possible effect on tau, which,
given the close connection between Rember and methylene blue, is
interesting.
******************************************************************************************** Rember:
Daily pill
that halts Alzheimer's is hailed as 'biggest breakthrough against disease for 100 years'
Daily Mail (UK)
By Jenny Hope
Last updated at 11:57 PM on 29th July 2008
(excerpts:)
"A new drug halts the devastating progress of Alzheimer's disease, say
British scientists.
"It is said to be more than twice as effective as current treatments.
"A daily capsule of rember [sic], as the drug is known, stops
Alzheimer's disease progressing by as much as 81 per cent, according to
trial results.
"Patients with the brain disorder had no significant decline in their
mental function over a 19-month period.
"It is the first time medication has been developed to target the
`tangles' in the brain that destroy nerve cells, leading to
deteriorating memory.
errrr... no it isn't the "first time". The
"water soluble component of common cinnamon" identified by Prof. Graves
at the University of California in Santa Barbara also "inhibits the
aggregation of tau and disassembles fibers that have already formed".
If this drug from the UK works, and I certainly hope that it does, then
the water-soluble cinnamon extract should too. And we have anecdotal
evidence that it does.
What this means is, don't despair that you can't get this new wonder
drug. You have alternatives! Check out cinnamon proanthocyanidins
and niacinamide.
Rember for Alzheimer's: Methylene
Blue's Comeback
corante.com
July
31,
2008
"Methylene blue has been around forever, used for urinary tract
infections, malaria, and all sorts of things, up to treating protozoal
infections in fish tanks. (For that matter, it's turned up over the
years as a surreptitious additive to blueberry pies and the like,
turning the unsuspecting consumer's urine greenish/blue, generally to
their great alarm: a storied med school prank from the old days)." http://pipeline.corante.com/archives/2008/07/31/rember_for_alzheimers_methylene_blues_comeback.php
Vienna (and Burkina Faso): What's New
With Methylene Blue?
Alzheimer Research Forum
30 July 2009
At ICAD in Vienna, Wischik discussed further analysis of the same Phase
2 trial of RemberTM, his biotech company's patented formulation of
methylene blue. Wischik noted in his talk that the company had patented
a new form called leuco-methylthioninium or LMT, which is no longer
blue and renders the drug more bioavailable and less toxic at higher
doses. For their part, Schirmer's group had characterized a reduced
white version of methylene blue (called leucoMB or methylene white) as
a possibly superior form of this drug for use in a colorless drug syrup
to treat malaria (see Buchholz et al., 2008 and Schirmer essay).
TauRx's new formulation is presently undergoing preclinical studies.
For a detailed first-person account of what happened with the high dose
of RemberTM in the Phase 2 trial and related topics... http://www.alzforum.org/new/detail.asp?id=2203
Protein
Inhibitor
Helps
Rid
Brain
Of
Toxic
Tau Protein
ScienceDaily (Sep. 30, 2009)
Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a
protein associated with Alzheimer's disease when it builds up
abnormally inside nerve cells affecting memory, neuroscientists at the
University of South Florida found. The study is reported online
September 29 in the Journal of Neuroscience...
One of the more effective Hsp70-inhibitor drugs the researchers
discovered was a derivative of methylthioninium chloride, or Rember™,
the first experimental medication reported to directly attack the tau
tangles in patients with Alzheimer's disease. Rember™ was heralded as a
major development in the fight against Alzheimer's when results in
early clinical trials were announced last year at the International
Conference on Alzheimer's disease.
But Rember™ and its derivatives do have some inherent problems; they're
not very potent so effective therapy would require fairly high doses,
Dickey said.
"The drug does help prevent the protein (tau) from clumping together,
but that in itself doesn't mean it's actively getting rid of the toxic
tau," he said. "Now that we know Hsp70 is a target of Rember™, we can
develop similarly-acting drugs that will more specifically target this
chaperone protein in affected areas of the brain, resulting in fewer
side effects."... http://www.sciencedaily.com/releases/2009/09/090929181808.htm
Protein inhibitor helps rid brain of
toxic tau protein
University of South Florida Health
[press release]
Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a
protein associated with Alzheimer's disease when it accumulates as
memory-choking tangles. One of the more effective Hsp70-inhibitor drugs
was a derivative of methylthioninium chloride, or Rember, the
laboratory study by neuroscientists at the University of South Florida
found.
Chemical Manipulation of Hsp70 ATPase
Activity Regulates Tau Stability
The Journal of Neuroscience
September 30, 2009
Alzheimer's disease and other tauopathies have recently been clustered
with a group of nervous system disorders termed protein misfolding
diseases. The common element established between these disorders is
their requirement for processing by the chaperone complex. It is now
clear that the individual components of the chaperone system, such as
Hsp70 and Hsp90, exist in an intricate signaling network that exerts
pleiotropic effects on a host of substrates. Therefore, we have
endeavored to identify new compounds that can specifically regulate
individual components of the chaperone family. Here, we hypothesized
that chemical manipulation of Hsp70 ATPase activity, a target that has
not previously been pursued, could illuminate a new pathway toward
chaperone-based therapies. Using a newly developed high-throughput
screening system, we identified inhibitors and activators of Hsp70
enzymatic activity. Inhibitors led to rapid proteasome-dependent tau
degradation in a cell-based model. Conversely, Hsp70 activators
preserved tau levels in the same system. Hsp70 inhibition did not
result in general protein degradation, nor did it induce a heat shock
response. We also found that inhibiting Hsp70 ATPase activity after
increasing its expression levels facilitated tau degradation at lower
doses, suggesting that we can combine genetic and pharmacologic
manipulation of Hsp70 to control the fate of bound substrates. Disease
relevance of this strategy was further established when tau levels were
rapidly and substantially reduced in brain tissue from tau transgenic
mice. These findings reveal an entirely novel path toward therapeutic
intervention of tauopathies by inhibition of the previously untargeted
ATPase activity of Hsp70.
The Journal of Neuroscience, 29(39):12079-12088;
doi:10.1523/JNEUROSCI.3345-09.2009
PubMed ID#: 19793966 http://www.jneurosci.org/cgi/content/abstract/29/39/12079
******************************************************************************************** A note about the links in this site:
The Internet is alive. From time to time, Web page administrators
will change links to pages, move things around, and delete stuff.
This can be very frustrating to a person viewing a page like this one
since if the author does not continuously update his site and check all
the links, interesting, useful and important information may no longer
be available. Sometimes, old copies of what used to be at a Web
site are archived at [give like, “waybackmachine”?] or Google sometimes
has a "cache" copy when you do a search. I have tried to include
enough of an excerpt of the original web document to be able to find it
should the link I provide become invalid.
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