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

Tiago Fleming Outeiro, 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

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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.

Original languageEnglish (US)
Pages (from-to)516-519
Number of pages4
JournalScience
Volume317
Issue number5837
DOIs
StatePublished - Jul 27 2007

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Cite this

Outeiro, T. F., Kontopoulos, E., Altmann, S. M., Kufareva, I., Strathearn, K. E., Amore, A. M., Volk, C. B., Maxwell, M. M., Rochet, J. C., McLean, P. J., Young, A. B., Abagyan, R., Feany, M. B., Hyman, B. T., & Kazantsev, A. G. (2007). Sirtuin 2 inhibitors rescue α-synuclein-mediated toxicity in models of Parkinson's disease. Science, 317(5837), 516-519. https://doi.org/10.1126/science.1143780