Cell Biology and Pathophysiology of α-Synuclein

  • Cold Spring Harb Perspect Med. 2018 Mar 1;8(3):a024091. doi: 10.1101/cshperspect.a024091.
Jacqueline Burré  1 ,  Manu Sharma  1 ,  Thomas C Südhof  2  3
Affiliations
  • 1. Appel Institute for Alzheimer's Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021.
  • 2. Departments of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305.
  • 3. Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305.
PMID: 28108534 DOI: 10.1101/cshperspect.a024091
Abstract

α-synuclein is an abundant neuronal protein that is highly enriched in presynaptic nerve terminals. Genetics and neuropathology studies link α-synuclein to Parkinson's disease (PD) and Other neurodegenerative disorders. Accumulation of misfolded oligomers and larger aggregates of α-synuclein defines multiple neurodegenerative diseases called synucleinopathies, but the mechanisms by which α-synuclein acts in neurodegeneration are unknown. Moreover, the normal cellular function of α-synuclein remains debated. In this perspective, we review the structural characteristics of α-synuclein, its developmental expression pattern, its cellular and subcellular localization, and its function in neurons. We also discuss recent progress on secretion of α-synuclein, which may contribute to its interneuronal spread in a prion-like fashion, and describe the neurotoxic effects of α-synuclein that are thought to be responsible for its role in neurodegeneration.

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