Resveratrol effective in lowering amyloid-beta peptides

Nov 7 2005

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 disease.

"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 in mice."

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.

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