Cell Biology and Pathophysiology of α-Synuclein
- 1Appel Institute for Alzheimer’s Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021
- 2Departments of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305
- 3Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305
- Correspondence: jab2058{at}med.cornell.edu; mas2189{at}med.cornell.edu
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.
