α-Synuclein impairs macroautophagy: implications for Parkinson’s disease
University of Cambridge · Institute for Medical Research · +2 more institutions
Abstract
Parkinson's disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplication of the α-synuclein gene locus increases α-synuclein expression and causes PD. Thus, overexpression of wild-type α-synuclein is toxic. In this study, we demonstrate that α-synuclein overexpression impairs macroautophagy in mammalian cells and in transgenic mice. Our data show that α-synuclein compromises autophagy via Rab1a inhibition and Rab1a overexpression rescues the autophagy defect caused by α-synuclein. Inhibition of autophagy by α-synuclein overexpression or Rab1a knockdown causes mislocalization of the autophagy protein, Atg9, and decreases omegasome…
Citation impact
- FWCI
- 26.39
- Percentile
- 100%
- References
- 54
Authors
13- ARAshley R. WinslowCorresponding
University of Cambridge, Institute for Medical Research
- CCChien‐Wen Chen
University of Cambridge, Institute for Medical Research
- SCSilvia Corrochano
Mary Lyon Centre at MRC Harwell, Medical Research Council
- AAAbraham Acevedo‐Arozena
Mary Lyon Centre at MRC Harwell, Medical Research Council
- DEDavid E. Gordon
University of Cambridge, Institute for Medical Research
Topics & keywords
- Autophagy
- Biology
- Cell biology
- Gene knockdown
- Alpha-synuclein
- Parkinson's disease
- Autophagosome
- Gene