Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease

  • Science. 2007 Jul 27;317(5837):516-9. doi: 10.1126/science.1143780.
Tiago Fleming Outeiro  1 ,  Eirene Kontopoulos ,  Stephen M Altmann ,  Irina Kufareva ,  Katherine E Strathearn ,  Allison M Amore ,  Catherine B Volk ,  Michele M Maxwell ,  Jean-Christophe Rochet ,  Pamela J McLean ,  Anne B Young ,  Ruben Abagyan ,  Mel B Feany ,  Bradley T Hyman ,  Aleksey G Kazantsev
Affiliations
  • 1. Alzheimer's Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA.
PMID: 17588900 DOI: 10.1126/science.1143780
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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