title: Cell Biology and Pathophysiology of α-Synuclein.
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.
authors.affiliation: Appel Institute for Alzheimer's Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Burré
authors.affiliation: Appel Institute for Alzheimer's Disease Research, Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York 10021.
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Departments of Molecular and Cellular Physiology, Stanford University Medical School, Stanford, California 94305.|Howard Hughes Medical Institute, Stanford University Medical School, Stanford, California 94305.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D051844:alpha-Synuclein / Q000737:chemistry* / Q000502:physiology*
chemical_list: D051844:alpha-Synuclein