Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease
2007 | journal article
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Outeiro, T. F., Kontopoulos, E., Altmann, S. M., Kufareva, I., Strathearn, K. E., Amore, A. M., Volk, C. B. ... Kazantsev, A. G. (2007). Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease. Science, 317(5837), 516-519. doi: https://doi.org/10.1126/science.1143780
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Details
- 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
