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

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

Affiliation

  • 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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