Alpha-synuclein structure and Parkinson's disease - lessons and emerging principles

Mol Neurodegener. 2019 Jul 22;14(1):29. doi: 10.1186/s13024-019-0329-1.

Richard M Meade ¹, David P Fairlie ², Jody M Mason ³ ⁴

Affiliations

1 Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
2 Division of Chemistry and Structural Biology, Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia.
3 Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK. [email protected].
4 Division of Chemistry and Structural Biology, Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, 4072, Australia. [email protected].

PMID: 31331359 DOI: 10.1186/s13024-019-0329-1

Abstract

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.

Keywords

Alpha-synuclein; Amyloid; CryoEM; Oligomers; Parkinson’s disease; Protein-protein interactions.

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