Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease
Scripps Research Institute · Brigham and Women's Hospital · +3 more institutions
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.
Citation impact
- FWCI
- 32.54
- Percentile
- 100%
- References
- 25
Authors
15- TFTiago F. Outeiro
Scripps Research Institute, Brigham and Women's Hospital, Harvard University, Purdue University West Lafayette, Massachusetts General Hospital
- EKEirene KontopoulosCorresponding
Scripps Research Institute, Brigham and Women's Hospital, Harvard University, Purdue University West Lafayette, Massachusetts General Hospital
- SMStephen M. AltmannCorresponding
Scripps Research Institute, Brigham and Women's Hospital, Harvard University, Purdue University West Lafayette, Massachusetts General Hospital
- IKIrina Kufareva
Scripps Research Institute, Brigham and Women's Hospital, Harvard University, Purdue University West Lafayette, Massachusetts General Hospital
- KEKatherine E. Strathearn
Scripps Research Institute, Brigham and Women's Hospital, Harvard University, Purdue University West Lafayette, Massachusetts General Hospital
Topics & keywords
- SIRT2
- Sirtuin
- Neurodegeneration
- Alpha-synuclein
- Histone deacetylase
- Biology
- Parkinson's disease
- Sirtuin 1
- Good health and well-being