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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7697105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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