Friday, November 6, 2009

Red Wine as effective weapon against Alzheimer’s Disease

Scientists call it the "French paradox" — a society that, despite consuming food high in cholesterol and saturated fats, has long had low death rates from heart disease. Research has suggested it is the red wine consumed with all that fatty food that may be beneficial — and not only for cardiovascular health but in warding off certain tumors and even Alzheimer's disease. So, red wine, together with Coffee and Marijuana, appears to be a strong natural weapon against merciless illness.

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Alzheimer's researchers at UCLA, in collaboration with Mt. Sinai School of Medicine in New York, have offered a framework mechanism on how red wine may actually reduce the incidence of the disease. Reporting in the Nov. 21, 2008 issue of the Journal of Biological Chemistry, David Teplow, a UCLA professor of neurology, and colleagues show how naturally occurring compounds in red wine called polyphenols block the formation of proteins that build the toxic plaques thought to destroy brain cells, and further, how they reduce the toxicity of existing plaques, thus reducing cognitive deterioration.

Polyphenols comprise a chemical class with more than 8,000 members, many of which are found in high concentrations in wine, tea, nuts, berries, cocoa and various plants. Past research has suggested that such polyphenols may inhibit or prevent the buildup of toxic fibers composed primarily of two proteins — Aß40 and Aß42 — that deposit in the brain and form the plaques which have long been associated with Alzheimer's. Until now, however, no one understood the mechanics of how polyphenols worked.

Teplow's lab has been studying how amyloid beta (Aß) is involved in causing Alzheimer's. In this work, researchers monitored how Aß40 and Aß42 proteins folded up and stuck to each other to produce aggregates that killed nerve cells in mice. They then treated the proteins with a polyphenol compound extracted from grape seeds. They discovered that polyphenols carried a one-two punch: They blocked the formation of the toxic aggregates of Aß and also decreased toxicity when they were combined with Aß before it was added to brain cells.

"What we found is pretty straightforward," Teplow said. "If the Aß proteins can't assemble, toxic aggregates can't form, and thus there is no toxicity. Our work in the laboratory, and Mt. Sinai's Dr. Giulio Pasinetti's work in mice, suggest that administration of the compound to Alzheimer's patients might block the development of these toxic aggregates, prevent disease development and also ameliorate existing disease."

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The researchers, from Mount Sinai School of Medicine, studied Mice, which were portraying alterations in the brain akin to Alzheimer's in 2006. The mice were fed with doses of Cabernet Sauvignon. It was observed that benefits of red wine was noticeably higher than the effects of ethanol or water; the mice showed remarkable reduction in the trademark alterations associated with memory in Alzheimer's disease. Indeed, Cabernet Sauvignon's contribution is crucial, preventing plaque accumulation in the brain, a distinguishing feature in the development of Alzheimer’s.

Researchers Dr. Giulio Maria Pasinetti and Dr. Jun Wang said "This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia."

Scientists at The Feinstein Institute for Medical Research have performed their own investigation on how and why a substance in red grapes and red wine lowers amyloid beta levels that accumulate in the brains of Alzheimer’s patients. Medicines targeting amyloid beta (Abeta) that make up the clumps in the hallmark plaques are now in many phases of experimental testing. The hope is that clearing out amyloid beta before it accumulates could stave off the disease and reduce symptoms.

Scientists at the Feinstein hope to develop this natural substance, called resveratrol, for the treatment of Alzheimer’s. Valorie Vingtdeux, PhD, and her colleagues have discovered that a specific protein —AMPK — controls Abeta levels. AMPK is interesting because it is a metabolic sensor in the cells and throughout the body. It senses levels of ATP, the body’s fuel source. When ATP levels drop, AMPK is activated to prepare the cells to adjust to the metabolic change in the body when fuel is low. It’s like a driver moving along at 50 miles per hour and slowing down when there is trouble ahead. Resveratrol activates AMPK, and in turn this protein lowers Abeta levels. Dr. Vingtdeux has presented these findings at the Society for Neuroscience in Washington, DC. The work has been done so far in cell culture, but Philippe Marambaud, PhD, who oversees the research, said there is every reason to believe that a similar process takes place in nature. “We hope that this result will translate into beneficial effects for Alzheimer’s patients someday,” said Dr. Marambaud. This is an important finding because the scientists identified a new potential molecular target — AMPK — to lower Abeta levels in Alzheimer’s.

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