Alpha-synuclein structure and Parkinson’s disease – lessons and emerging principles

• Published in: Molecular neurodegeneration Vol. 14; no. 1; pp. 29 - 14
• Main Authors: Meade, Richard M., Fairlie, David P., Mason, Jody M.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.07.2019; BioMed Central; BMC
• Subjects: Alpha-synuclein; alpha-Synuclein - metabolism; Amyloid; Brain - pathology; Care and treatment; CryoEM; Development and progression; Humans; Lewy Bodies - metabolism; Lewy Body Disease - metabolism; Membrane proteins; Multiple system atrophy; Multiple System Atrophy - metabolism; Multiple System Atrophy - pathology; Nuclear magnetic resonance; Oligomers; Parkinson disease; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson’s disease; Phenotypes; Protein-protein interactions; Review; Oligomers; Amyloid; Alpha-synuclein; CryoEM; Parkinson’s disease; Protein-protein interactions
• ISSN: 1750-1326; 1750-1326
• DOI: 10.1186/s13024-019-0329-1

Alpha-synuclein (αS) is the major constituent of Lewy bodies and a pathogenic hallmark of all synucleinopathathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). All diseases are determined by αS aggregate deposition but can be separated into distinct pathological phenotypes and diagnostic criteria. Here we attempt to reinterpret the literature, particularly in terms of how αS structure may relate to pathology. We do so in the context of a rapidly evolving field, taking into account newly revealed structural information on both native and pathogenic forms of the αS protein, including recent solid state NMR and cryoEM fibril structures. We discuss how these new findings impact on current understanding of αS and PD, and where this information may direct the field.