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

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Authors

Tiago F. Outeiro · Purdue University West Lafayette

Eirene Kontopoulos · Scripps Research Institute

Stephen M. Altmann · Purdue University West Lafayette

Irina Kufareva · Scripps Research Institute

Katherine E. Strathearn · Purdue University West Lafayette

Allison Amore · Scripps Research Institute

Catherine B. Volk

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.

Topics & Keywords

Sirtuins and Resveratrol in Medicine Parkinson's Disease Mechanisms and Treatments Genetic Neurodegenerative Diseases

UN Sustainable Development Goals

Good health and well-being

Publication Details

Published in: Science

Volume 317, Issue 5837, pp. 516-519

DOI: 10.1126/science.1143780

Field-Weighted Citation Impact: 32.06