It is well established that a progressive loss of neurons with age underlies a variety of debilitating neurological disorders including Alzheimer's Disease and Amyotrophic Lateral Sclerosis (ALS), neurodegenerative diseases which have been associated with reduced mitochondrial function. Sirtuins are a recently discovered class of enzymes that appear to affect the aging process in mammals and increase the number and function of mitochondria.
According to the findings in this paper, resveratrol, a SIRT1 activator, reduced the loss of neuronal function in the brain (hippocampus) and prevented learning impairment in a well established animal model of Alzheimer's Disease. This response was associated with SIRT1 dependent deacetylation of PGC1a. Resveratrol also promoted neuronal survival in cell based models of Alzheimer's Disease and ALS.
The three senior authors of the EMBO article include Sirtris co-founder and co-chair of the Scientific Advisory Board (SAB), David A. Sinclair, Ph.D., Department of Pathology and Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, and Sirtris SAB members Li-Huei Tsai , Ph.D. Howard Hughes Medical Institute, Picower Institute for Learning and Memory, Massachusetts Institute of Technology and Pere Puigserver, Ph.D., Dana Farber Cancer Institute and Department of Cell Biology, Harvard Medical School.
"This work is significant because it shows that a SIRT1 activator can protect against neurodegeneration, highlighting the therapeutic potential of SIRT1 activators," said David Sinclair.
Christoph Westphal, M.D., Ph.D., Chief Executive Officer of Sirtris Pharmaceuticals added "These new data support our belief in SIRT1 as a therapeutic target for neurodegenerative disease, which expands the potential of our pipeline of SIRT1 modulators designed to treat a number of diseases of aging such as metabolic and mitochondrial disorders, and now neurological disorders."
Online copies of the article can be obtained at: http://www.nature.com/emboj
About Sirtris Pharmaceuticals
Sirtris Pharmaceuticals is a biopharmaceutical company focused on discovering and developing proprietary, orally available, small molecule drugs with the potential to treat diseases associated with aging, including metabolic diseases such as Type 2 Diabetes. Our drug candidates are designed to mimic certain beneficial health effects of calorie restriction, without requiring a change in eating habits, by activation of sirtuins, a recently discovered class of enzymes that control the aging process. The company's headquarters are in Cambridge, Massachusetts.
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