A study published in
the November 11 issue of the Journal of Biological Chemistry
shows that resveratrol, a compound found in grapes and
red wine, lowers the levels of the amyloid-beta peptides
which cause the telltale senile plaques of Alzheimer's
"Resveratrol is a natural
polyphenol occurring in abundance in several plants, including
grapes, berries and peanuts," explains study author
Philippe Marambaud. "The polyphenol is found in high
concentrations in red wines. The highest concentration
of resveratrol has been reported in wines prepared from
Pinot Noir grapes. Generally, white wines contain 1% to
5% of the resveratrol content present in most red wines."
One of the characteristic features
of Alzheimer's disease is the deposition of amyloid-beta
peptides in the brain. Philippe Marambaud and his colleagues
at the Litwin-Zucker Research Center for the Study of
Alzheimer's Disease and Memory Disorders in Manhasset,
New York, administered resveratrol to cells which produce
human amyloid-beta and tested the compound's effectiveness
by monitoring amyloid-beta levels inside and outside the
cells. They found that levels of amyloid-beta in the treated
cells were much lower than those in untreated cells.
The researchers believe the compound
acts by stimulating the degradation of amyloid-beta peptides
by the proteasome, a barrel-shaped multi-protein complex
that can specifically digest proteins into short polypeptides
and amino acids.
However, eating grapes may not
be a cure for Alzheimer's disease. "It is difficult
to know whether the anti-amyloidogenic effect of resveratrol
observed in cell culture systems can support the beneficial
effect of specific diets such as eating grapes,"
cautions Marambaud. "Resveratrol in grapes may never
reach the concentrations required to obtain the effect
observed in our studies. Grapes and wine however contain
more than 600 different components, including well-characterized
antioxidant molecules. Therefore, we cannot exclude the
possibility that several compounds work in synergy with
small amounts of resveratrol to slow down the progression
of the neurodegenerative process in humans."
Following up on their studies,
Marambaud and his colleagues are trying to figure out
how resveratrol exerts its effects in order to develop
similar compounds to use in fighting Alzheimer's disease.
"Our long-term goal is now to elucidate the exact
molecular mechanisms involved in the beneficial properties
of resveratrol as a necessary prerequisite to the identification
of novel molecular targets and therapeutic approaches,"
says Marambaud. "The observation that resveratrol
has a strong anti-amyloidogenic activity is a powerful
starting point for screening analogues of resveratrol
for more active and more stable compounds, a task in which
our laboratory is actively involved. We have already obtained
analogues of resveratrol that are 20 times more potent
than the original natural compound. We are now aiming
to find more stable analogues and to test them in vivo
Additional good news is that resveratrol
may also be effective in fighting other human amyloid-related
diseases such as Huntington's, Parkinson's and prion diseases.
Studies by a group at the Institut National de la Santé
et de la Recherche Médicale in Paris, France headed
by Christian Néri have recently shown that resveratrol
may protect neurons against amyloid-like polyglutamines,
a hallmark of Huntington's disease.
Reference Source 128