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Archive - Feb 11, 2012

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Study Reveals Probable Mechanism Underlying Resveratrol Activity

National Institutes of Health researchers and their colleagues have identified how resveratrol, a naturally occurring chemical found in red wine and other plant products, may confer its health benefits. The authors present evidence that resveratrol does not directly activate sirtuin 1, a protein associated with aging. Rather, the authors found that resveratrol inhibits certain types of proteins known as phosphodiesterases (PDEs), enzymes that help regulate cell energy. These findings may help settle the debate regarding resveratrol's biochemistry and pave the way for resveratrol-based medicines. The chemical has received significant interest from pharmaceutical companies for its potential to combat diabetes, inflammation, and cancer. The study appears in the February 3, 2012 issue of Cell. "Resveratrol has potential as a therapy for diverse diseases such as type 2 diabetes, Alzheimer's disease, and heart disease," said lead study author Dr. Jay H. Chung, chief of the Laboratory of Obesity and Aging Research at the NIH's National Heart, Lung, and Blood Institute. "However, before researchers can transform resveratrol into a safe and effective medicine, they need to know exactly what it targets in cells." Several previous studies suggested that resveratrol's primary target is sirtuin 1. Dr. Chung and colleagues suspected otherwise when they found that resveratrol activity required another protein called AMPK. This would not be the case if resveratrol directly interacted with sirtuin 1. In the current study, the researchers methodically traced out the metabolic activity in cells treated with resveratrol and identified PDE4 in the skeletal muscle as the principal target for the health benefits of resveratrol. By inhibiting PDE4, resveratrol triggers a series of events in a cell, one of which indirectly activates sirtuin 1.

Nervous System Wiring May Rely on Just a Handful of Genes and Proteins

Researchers at the Salk Institute have discovered a startling feature of early brain development that helps to explain how complex neuron wiring patterns are programmed using just a handful of critical genes. The findings, published in the February 3, 2012 issue of Cell, may help scientists develop new therapies for neurological disorders, such as amyotrophic lateral sclerosis (ALS), and provide insight into certain cancers. The Salk researchers discovered that only a few proteins on the leading edge of a motor neuron's axon - its outgoing electrical "wire" - and within the extracellular soup it travels through, guide the nerve as it emerges from the spinal cord. These molecules can attract or repel the axon, depending on the long and winding path it must take to finally connect with its target muscle. "The budding neuron has to detect the local environment it is growing through and decide where it is, and whether to grow straight, move to the left or right, or stop," says the study's senior investigator, Dr. Sam Pfaff, a professor in Salk's Gene Expression Laboratory and a Howard Hughes Medical Institute investigator. "It does this by mixing and matching just a handful of protein products to create complexes that tell a growing neuron which way to go, in the same way that a car uses the GPS signals it receives to guide it through an unfamiliar city," he says. The brain contains millions of times the number of neuron connections than the number of genes found in the DNA of brain cells. This is one of the first studies to try and understand how a growing neuron integrates many different pieces of information in order to navigate to its eventual target and make a functional connection.