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Rejected drug may protect against toxic substance common to Alzheimer's and Parkinson's diseases
Date:8/13/2012

umab trial has failed might only help patients if begun before the brain pathology begins to build up."

In the new study, the researchers administered the drug to three different systems: yeast, mice and mammal cells all showing build-up of alpha-synuclein, a protein known to cause neurodegeneration. In all three systems, they determined that latrepiridine activated autophagy, the so-called "self-eating" process of cells that protects the brain from neurodegeneration, which targeted synuclein and protected against its toxicity. In mice, the drug reduced the amount of synuclein accumulated in the brain through autophagy.

John Steele, PhD, a Mount Sinai neuroscience graduate student, devoted his PhD thesis to these studies. Lenard Lachenmayer, MD, a postdoctoral fellow working under the supervision of Zhenyu Yue, PhD, Associate Professor of Neurology at Mount Sinai, shares first authorship of the new paper with Steele and with Shulin Ju, PhD, a postdoctoral fellow at Brandeis University working under the direction of Greg Petsko, PhD, and Dagmar Ringe, PhD, both professors of biochemistry, chemistry and neuroscience at Brandeis.

This study is the second of two published by Dr. Gandy's team in Molecular Psychiatry. The first, published July 31, 2012, determined that latrepiridine stopped the toxicity of amyloid-beta protein accumulation in mice present with Alzheimer's disease by inducing autophagy. In that study, they randomly administered either latrepirdine or placebo to mice engineered to have the early stages of Alzheimer's disease and found that, through autophagy, the drug improved memory.

Dr. Petsko, an expert in protein structure who is now Professor of Neurology and Neuroscience at Weill Cornell Medical College, noted that, surprisingly, latrepirdine protects yeast cells from the toxicity of alpha-synuclein while leaving the cells vulnerable to killing by either the Huntington's disease protein or by either of the
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Contact: Mount Sinai Press Office
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The Mount Sinai Hospital / Mount Sinai School of Medicine
Source:Eurekalert

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