Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease
Tiago F. Outeiro(Scripps Research Institute), Eirene Kontopoulos(Scripps Research Institute), Stephen M. Altmann(Scripps Research Institute), Irina Kufareva(Scripps Research Institute), Katherine E. Strathearn(Scripps Research Institute), Allison Amore(Scripps Research Institute), Catherine B. Volk(Scripps Research Institute), Michele M. Maxwell(Scripps Research Institute), Jean‐Christophe Rochet(Scripps Research Institute), Pamela J. McLean(Scripps Research Institute), Anne B. Young(Scripps Research Institute), Ruben Abagyan(Scripps Research Institute), Mel Β. Feany(Scripps Research Institute), Bradley T. Hyman(Scripps Research Institute), Aleksey Kazantsev(Scripps Research Institute)
Cited by 1,055Open Access
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.
Related Papers
No related papers found
Powered by citation graph analysis