Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease - PubMed (original) (raw)

. 2007 Jul 27;317(5837):516-9.

doi: 10.1126/science.1143780. Epub 2007 Jun 21.

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

• PMID: 17588900
• DOI: 10.1126/science.1143780

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

Tiago Fleming Outeiro et al. Science. 2007.

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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Comment in

• Medicine. The yin-yang of sirtuins.
  Dillin A, Kelly JW. Dillin A, et al. Science. 2007 Jul 27;317(5837):461-2. doi: 10.1126/science.1146585. Science. 2007. PMID: 17656709 No abstract available.

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