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The Role of α-Synuclein Oligomers in Parkinson’s Disease

Du, Xiao-yu, Xie, Xi-xiu, Liu, Rui-tian·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21228645PMC PMC7697105
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Abstract

α-synuclein (α-syn) is a protein associated with the pathogenesis of Parkinson’s disease (PD), the second most common neurodegeneration disease with no effective treatment. However, how α-syn drives the pathology of PD remains elusive. Recent studies suggest that α-syn oligomers are the primary cause of neurotoxicity and play a critical role in PD. In this review, we discuss the process of α-syn oligomers formation and the current understanding of the structures of oligomers. We also describe seed and propagation effects of oligomeric forms of α-syn. Then, we summarize the mechanism by which α-syn oligomers exert neurotoxicity and promote neurodegeneration, including mitochondrial dysfunction, endoplasmic reticulum stress, proteostasis dysregulation, synaptic impairment, cell apoptosis and neuroinflammation. Finally, we investigate treatment regimens targeting α-syn oligomers at present. Further research is needed to understand the structure and toxicity mechanism of different types of oligomers, so as to provide theoretical basis for the treatment of PD.

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Metadata

Authors
Du, X.-Y., Xie, X.-X., & Liu, R.-T.
Affiliations
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Haidian District, Beijing 100190, China
ORCID
Liu, Rui-tian
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-11-17
Volume
21
Issue
22
Pages
8645
ISSN
1422-0067
DOI
10.3390/ijms21228645
PMC
PMC7697105
Cited by
234
References
14
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
National Natural Science Foundation of China (81971073, 81903531)

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