Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease

2007 | journal article

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​Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease​
Outeiro, T. F. ; Kontopoulos, E.; Altmann, S. M.; Kufareva, I.; Strathearn, K. E.; Amore, A. M. & Volk, C. B. et al.​ (2007) 
Science317(5837) pp. 516​-519​.​ DOI: https://doi.org/10.1126/science.1143780 

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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.; Kazantsev, Aleksey G.
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 α-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued α-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.
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 α-synuclein toxicity and modified inclusion morphology in a cellular model of Parkinson's disease. Genetic inhibition of SIRT2 via small interfering RNA similarly rescued α-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.
Issue Date
2007
Journal
Science 
ISSN
0036-8075
eISSN
1095-9203
Language
English

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