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Updated: Jul 14, 2026

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
Published on: November 11, 2014
Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease
Tiago Fleming Outeiro1, Eirene Kontopoulos, Stephen M Altmann
1Alzheimer's Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA.
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.
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