Alpha-Synuclein Structure and Parkinson's Disease – Lessons and Emerging Principles

Richard Meade, David P. Fairlie, Jody Mason

Research output: Contribution to journalArticle

Abstract

Alpha-synuclein (aS) 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 aS 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 aS 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 aS protein, including recent solid state NMR and cryoEM fibril structures. We discuss how these new findings impact on current understanding of aS and PD, and where this information may direct the field.
Original languageEnglish
JournalMolecular Neurodegeneration
DOIs
Publication statusAccepted/In press - 15 Jun 2019

Keywords

  • Alpha-synuclein
  • CryoEM
  • protein-protein interactions
  • Parkinson’s disease
  • oligomers
  • Amyloid

Cite this

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abstract = "Alpha-synuclein (aS) 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 aS 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 aS 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 aS protein, including recent solid state NMR and cryoEM fibril structures. We discuss how these new findings impact on current understanding of aS and PD, and where this information may direct the field.",
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AB - Alpha-synuclein (aS) 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 aS 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 aS 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 aS protein, including recent solid state NMR and cryoEM fibril structures. We discuss how these new findings impact on current understanding of aS and PD, and where this information may direct the field.

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KW - protein-protein interactions

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KW - oligomers

KW - Amyloid

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