Science 27 July 2007:
Vol. 317. no. 5837, pp. 516 - 519
DOI: 10.1126/science.1143780


Sirtuin 2 Inhibitors Rescue {alpha}-Synuclein-Mediated Toxicity in Models of Parkinson's Disease

Tiago Fleming Outeiro,1,2 Eirene Kontopoulos,3* Stephen M. Altmann,2* Irina Kufareva,4 Katherine E. Strathearn,5 Allison M. Amore,2 Catherine B. Volk,5 Michele M. Maxwell,2 Jean-Christophe Rochet,5 Pamela J. McLean,1,2 Anne B. Young,2 Ruben Abagyan,4 Mel B. Feany,3 Bradley T. Hyman,1,2 Aleksey G. Kazantsev2{dagger}

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.

http://www.sciencemag.org/cgi/conten...i;317/5837/516