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Linking SIRT2 to Parkinson’s Disease

Adam L. Garske, †^§, Brian C. Smith, †^§ and John M. Denu, ‡*

^† Departments of Chemistry

^‡ Biomolecular Chemistry, University of Wisconsin–Madison, Madison, Wisconsin 53706

ACS Chem. Biol., 2007, 2 (8), pp 529–532

DOI: 10.1021/cb700160d

Publication Date (Web): August 17, 2007

These authors contributed equally to this work.

* Corresponding author, jmdenu@wisc.edu.

Abstract

A recent study has identified selective inhibitors of the human silent information regulator 2 NAD ⁺-dependent protein deacetylase, SIRT2, and has shown that these compounds protect against α-synuclein-mediated toxicity in cellular models of Parkinson’s disease. The inhibitors were found to ameliorate dopaminergic cell death in vitro and in a Drosophila model of Parkinson’s disease. Although the molecular mechanism of action is unclear, the compounds may function by promoting the formation of enlarged inclusion bodies, which are suggested to provide a cell-survival advantage.

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Received: July 31, 2007
Accepted: July 31, 2007

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Linking SIRT2 to Parkinson’s Disease