Journal
SCIENCE
Volume 317, Issue 5837, Pages 516-519Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1143780
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Funding
- NINDS NIH HHS [R01-NS049221, 5P50-NS38372A-06] Funding Source: Medline
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The sirtuins are members of the histone deacetylase family of proteins that participate in a variety of cellular functions and play a role in aging. We identified a potent inhibitor of sirtuin 2 ( SIRT2) and found that inhibition of SIRT2 rescued alpha-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued alpha-synuclein toxicity. Furthermore, the inhibitors protected against dopaminergic cell death both in vitro and in a Drosophila model of Parkinson's disease. The results suggest a link between neurodegeneration and aging.
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