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Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease |
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| Authors: | 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 |
| Affiliation: | Alzheimer's Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA. |
| 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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