title: Limelight on alpha-synuclein: pathological and mechanistic implications in neurodegeneration.
abstract: The pathogenesis of many neurodegenerative disorders arises in association with the misfolding and accumulation of a wide variety of proteins. Much emphasis has been placed on understanding the nature of these protein accumulations, including their composition, the process by which they are formed and the physiological impact they impose at cellular and, ultimately, organismal levels. Alpha-synuclein (ASYN) is the major component of protein inclusions known as Lewy bodies and Lewy neurites, which are the typical pathological hallmarks in disorders referred to as synucleinopathies. In addition, mutations or multiplications in the gene encoding for ASYN have also been shown to cause familial cases of PD, the most common synucleinopathy. Although the precise function of ASYN remains unclear, it appears to be involved in a vast array of cellular processes. Here, we review, in depth, a spectrum of cellular and molecular mechanisms that have been implicated in synucleinopathies. Importantly, detailed understanding of the biology/pathobiology of ASYN may enable the development of novel avenues for diagnosis and/or therapeutic intervention in synucleinopathies.
authors.affiliation: Department of NeuroDegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Goettingen, Waldweg, Goettingen, Germany.
authors.forename: Pauline
authors.initials: P
authors.lastname: Wales
authors.forename: Raquel
authors.initials: R
authors.lastname: Pinho
authors.forename: Diana F
authors.initials: DF
authors.lastname: Lázaro
authors.forename: Tiago F
authors.initials: TF
authors.lastname: Outeiro
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D016631:Lewy Bodies / Q000378:metabolism; D020961:Lewy Body Disease / Q000378:metabolism* / Q000628:therapy; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000628:therapy; D010300:Parkinson Disease / Q000378:metabolism* / Q000628:therapy; D010766:Phosphorylation; D054970:Pure Autonomic Failure / Q000378:metabolism* / Q000628:therapy; D009435:Synaptic Transmission / Q000502:physiology; D057149:Ubiquitinated Proteins / Q000378:metabolism; D054875:Ubiquitination; D051844:alpha-Synuclein / Q000378:metabolism*; D051846:beta-Synuclein / Q000378:metabolism; D051845:gamma-Synuclein / Q000378:metabolism
chemical_list: D057149:Ubiquitinated Proteins; D051844:alpha-Synuclein; D051846:beta-Synuclein; D051845:gamma-Synuclein
keywords: Alpha-synuclein; Lewy body; aggregation; neurodegeneration; synucleinopathies