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

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 caus...

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Autores principales: Du, Xiao-yu, Xie, Xi-xiu, Liu, Rui-tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697105/
https://www.ncbi.nlm.nih.gov/pubmed/33212758
http://dx.doi.org/10.3390/ijms21228645
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author Du, Xiao-yu
Xie, Xi-xiu
Liu, Rui-tian
author_facet Du, Xiao-yu
Xie, Xi-xiu
Liu, Rui-tian
author_sort Du, Xiao-yu
collection PubMed
description 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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spelling pubmed-76971052020-11-29 The Role of α-Synuclein Oligomers in Parkinson’s Disease Du, Xiao-yu Xie, Xi-xiu Liu, Rui-tian Int J Mol Sci Review 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. MDPI 2020-11-17 /pmc/articles/PMC7697105/ /pubmed/33212758 http://dx.doi.org/10.3390/ijms21228645 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Du, Xiao-yu
Xie, Xi-xiu
Liu, Rui-tian
The Role of α-Synuclein Oligomers in Parkinson’s Disease
title The Role of α-Synuclein Oligomers in Parkinson’s Disease
title_full The Role of α-Synuclein Oligomers in Parkinson’s Disease
title_fullStr The Role of α-Synuclein Oligomers in Parkinson’s Disease
title_full_unstemmed The Role of α-Synuclein Oligomers in Parkinson’s Disease
title_short The Role of α-Synuclein Oligomers in Parkinson’s Disease
title_sort role of α-synuclein oligomers in parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697105/
https://www.ncbi.nlm.nih.gov/pubmed/33212758
http://dx.doi.org/10.3390/ijms21228645
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