Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease-Reference-Cited by-同舟云学术

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

Published:2007-07-27 Issue:5837 Volume:317 Page:516-519
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Outeiro Tiago Fleming¹²³⁴⁵,Kontopoulos Eirene¹²³⁴⁵,Altmann Stephen M.¹²³⁴⁵,Kufareva Irina¹²³⁴⁵,Strathearn Katherine E.¹²³⁴⁵,Amore Allison M.¹²³⁴⁵,Volk Catherine B.¹²³⁴⁵,Maxwell Michele M.¹²³⁴⁵,Rochet Jean-Christophe¹²³⁴⁵,McLean Pamela J.¹²³⁴⁵,Young Anne B.¹²³⁴⁵,Abagyan Ruben¹²³⁴⁵,Feany Mel B.¹²³⁴⁵,Hyman Bradley T.¹²³⁴⁵,Kazantsev Aleksey G.¹²³⁴⁵

Affiliation:

1. Alzheimer's Research Unit, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA.

2. Mass General Institute for Neurodegenerative Disease, MGH, Harvard Medical School, CNY 114, 16th Street, Charlestown, MA 02129, USA.

3. Harvard Medical School and Brigham and Women's Hospital, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Harvard New Research Building, Room 630, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.

4. Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

5. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, 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 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference26 articles.

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4. α-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity

5. The Human Sir2 Ortholog, SIRT2, Is an NAD+-Dependent Tubulin Deacetylase

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