Resveratrol lowers peptide associated with Alzheimer’s disease

A report published in the November 11 2005 issue of the Journal of Biological Chemistry revealed that resveratrol, a compound found in red grapes and peanuts, reduces amyloid-beta peptide levels produced by specific brain cells. Deposits of amyloid-beta contribute to the plaques found in the brains of Alzheimer's disease patients which are believed to be responsible for much of the damage that occurs in this disease.

Philippe Marambaud and colleagues at the Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders in Manhasset, New York gave resveratrol to human amyloid-beta-producing cells and measured amyloid-beta levels inside and outside of the cells. They found that resveratrol, while not inhibiting amyloid-beta production, promoted its degradation, thereby lowering levels compared to those measured in untreated cells.

While grapes are one good source of resveratrol, eating them may not be an effective Alzheimer’s disease treatment. Dr Marambaud explained, "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. 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."

"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,” he added. "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."

Alzheimer’s disease

The most characteristic features of Alzheimer's disease are senile plaques of beta-amyloid peptide, neurofibrillary tangles involving tau protein, loss of synapses, and (ultimately) the death of neurons. Although neurofibrillary tangles are more closely associated with neuronal death than beta-amyloid, the evidence is becoming convincing that beta-amyloid is the factor most responsible for starting the degenerative processes of Alzheimer's disease.

Both neurofibrillary tangles and beta-amyloid senile plaques are due to protein abnormalities. The beta-amyloid peptide present in the core of senile plaques is a 42-amino acid chain produced by cleavage of a larger protein known as amyloid precursor protein (APP). There are at least three different types of beta-amyloid, depending on the site of RNA splicing/cleavage. APP is normally found embedded in neural membranes and is thought to contribute to stabilizing the contact points between synapses. Some aggregates of beta-amyloid accumulate throughout brain tissue in normal aging. Beta-amyloid is degraded by at least three enzymes which cleave it into smaller molecules. As it is cleaved and destroyed, more beta-amyloid is formed and accumulates. The damage begins when the beta-amyloid becomes concentrated in senile plaques and an inflammatory reaction with ongoing oxidative stress and free-radical damage ensues.

Ginkgo biloba is the world's oldest living tree. It has been traditionally used for improving memory and Alzheimer's disease. It is a powerful antioxidant and also functions as a mild vasodilator (improves circulation), anti-inflammatory (via antioxidant effects), membrane protector, antiplatelet agent, and neurotransmitter modulator (Perry et al. 1999; Diamond et al. 2000). Ginkgo was shown to protect neurons against toxicity induced by beta-amyloid fragments, with a maximal and complete protection at the highest concentration tested. Ginkgo also completely blocked beta-amyloid-induced events, such as reactive oxygen species accumulation (Bastianetto et al. 2000; Yao et al. 2001).

https://www.lifeextension.com/protocols/neurological/alzheimers-disease

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Life Extension magazine November 2005 issue

https://www.lifeextension.com/magazine/2005/11

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Dayna Dye
Editor, Life Extension Update
ddye@lifeextension.com
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