Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease by Outeiro Tiago Fleming, Kontopoulos Eirene, Altmann Stephen M, Kufareva Irina, Strathearn Katherine E, Amore Allison M, Volk Catherine B, Maxwell Michele M, Rochet Jean-Christophe, McLean Pamela J, Young Anne B, Abagyan Ruben, Feany Mel B, Hyman Bradley T, Kazantsev Aleksey G in Science (New York, N.Y.) (2007). PubMed

Abstract

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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