2012-03-31

#alzheimer's cured by anti-cancer drugs #health

3.21: news.health/alz/cured by anti-cancer drugs:

. epothilone D (EpoD) works like paclitaxel,
but it also crosses the blood-brain barrier,
bexarotene is another anti-cancer agent that
cures alzheimers in mice bred to develope alzheimers
or alz'-like symptoms .

. are these anti-cancer drugs working by controlling
sugar's ability to cross-link proteins?

Epothilones are Novel Anti-Tubulin Cytotoxic Agents .
Epothilones act via microtubule stabilization:
. after stabilization of microtubules,
the formation of the mitototic spindle is inhibited,
and the cell undergoes apoptosis.

uphs.upenn.edu's summary:
EpoD prevents cancer cell proliferation by
over-stabilizing specialized microtubules involved in the
separation of chromosomes during the process of cell division.
. in a mouse model of Alzheimer's disease (AD),
epothilone D (EpoD) is effective in
preventing further neurological damage
and improving cognitive performance:
. aged mice had memory deficits and a condition that resembles
the tangles formed by misfolded tau protein .
In nerve cells, tau normally stabilizes structures called microtubules,
the molecular railroad tracks upon which cellular cargo is transported.
Tangles may compromise microtubule stability
with resulting damage to nerve cells.

jneurosci.org's summary:
Neurodegenerative tau.opathies, such as Alzheimer's disease (AD),
are characterized by insoluble deposits of
hyper.phosphorylated tau protein within brain neurons.
Increased phosphorylation and decreased solubility
may diminish normal tau stabilization of microtubules (MTs).
EpoD treatment reduced axonal dystrophy
and increased axonal MT density
which led to improved cognitive performance.
Moreover, the EpoD-treated PS19 mice had
less forebrain tau pathology
and increased hippocampal neuronal integrity .

. another {anti-cancer, anti-alzheimer} coincidence
is that Bexarotene also cures both;
but appears to be doing so by a different route .
. while it controls cutaneous T-cell lymphoma by
activation of retinoid X receptors (RXRs);
it may be controlling alzheimer's amyloid plaque by
stimulating the expression of apolipoprotein E (ApoE)
which leads to intracellular clearance of β-Amyloid .

Apolipoprotein E (ApoE) :
. ApoE transports lipoproteins, fat-soluble vitamins, and cholesterol
into the lymph system and then into the blood.
It is essential for the normal catabolism of
triglyceride-rich lipoprotein constituents.
. found in the chylomicron and Intermediate-density lipoprotein
that binds to a specific receptor on liver cells and peripheral cells.
. it is suppressing T cell proliferation,
macrophage functioning regulation,
lipid antigen presentation facilitation (by CD1) to natural killer T cell
as well as modulation of inflammation and oxidation.
. ApoE also enhances proteolytic break-down of beta-amyloid,
both within and between cells;
but the E4 variant (isoform ApoE-ε4) is not very effective at this .
. carriers of 2 E4 alleles have 10 ... 30 times the risk of
developing AD by 75 years of age,
as compared to those not carrying any E4 alleles.

ApoE deficiency causes depleted myelin cholesterol;
statin therapy may result in Cholesterol Depletion;
both statins and ApoE deficiency can result in neuron failure
as can Alzheimer's disease .
The inhibition of liver-produced cholesterol is associated with
failure of cholesterol-rich lipid transport mechanisms
used by processes such as cell imports (endocytosis)
and cell exports (exocytosis).
. most substances important to cells are
large polar molecules that cannot pass through the
hydrophobic plasma or cell membrane;
therefore they rely on vesicles attaching to the membrane
to either import or export the reluctant molecules .
. cholesterol lowering drug can harm insulin function by
making pancreatic beta cells unable to export their insulin .
A retrospective analysis of a five year trial showed a
30% increase in the incidence of Diabetes
associated with a cholesterol reduction therapy .