www.perpetualcommotion.com
"Give with a free hand, but give only your own."
-- J.R.R. Tolkien The Children of Hurin
- Hsp70 -
General Information:
Names:
Wikipedia entry:
Dr. Ray Shahelien entry:
********************************************************************************************
Observations:
********************************************************************************************
Known sources:
********************************************************************************************
Natural sources:
********************************************************************************************
References:
Hsp70
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.
University of South Florida Health
http://www.eurekalert.org/pub_releases/2009-09/uosf-pih092809.php
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
********************************************************************************************
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Home
Preface Brain Failure Notes Notes II
References pg. 1 References pg. 2
Nutritional Alternatives
Patricia's Protocol
Tauopathy
Discussion
Forum
Correspondence Newsletters Poems Memory Enhancement
********************************************************************************************
Questions or comments, contact "perpetualcommotion.com" at gmail.com
Updated: July 25, 2012
Inception: July 25, 2012