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New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease

Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-he...

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Autores principales: Zhang, Guoxin, Xia, Yun, Wan, Fang, Ma, Kai, Guo, Xingfang, Kou, Liang, Yin, Sijia, Han, Chao, Liu, Ling, Huang, Jinsha, Xiong, Nian, Wang, Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261981/
https://www.ncbi.nlm.nih.gov/pubmed/30524265
http://dx.doi.org/10.3389/fnagi.2018.00370
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author Zhang, Guoxin
Xia, Yun
Wan, Fang
Ma, Kai
Guo, Xingfang
Kou, Liang
Yin, Sijia
Han, Chao
Liu, Ling
Huang, Jinsha
Xiong, Nian
Wang, Tao
author_facet Zhang, Guoxin
Xia, Yun
Wan, Fang
Ma, Kai
Guo, Xingfang
Kou, Liang
Yin, Sijia
Han, Chao
Liu, Ling
Huang, Jinsha
Xiong, Nian
Wang, Tao
author_sort Zhang, Guoxin
collection PubMed
description Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of “LB-like aggregates,” by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson’s pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials.
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spelling pubmed-62619812018-12-06 New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease Zhang, Guoxin Xia, Yun Wan, Fang Ma, Kai Guo, Xingfang Kou, Liang Yin, Sijia Han, Chao Liu, Ling Huang, Jinsha Xiong, Nian Wang, Tao Front Aging Neurosci Neuroscience Parkinson’s disease (PD) is one of the synucleinopathies spectrum of disorders typified by the presence of intraneuronal protein inclusions. It is primarily composed of misfolded and aggregated forms of alpha-synuclein (α-syn), the toxicity of which has been attributed to the transition from an α-helical conformation to a β-sheetrich structure that polymerizes to form toxic oligomers. This could spread and initiate the formation of “LB-like aggregates,” by transcellular mechanisms with seeding and subsequent permissive templating. This hypothesis postulates that α-syn is a prion-like pathological agent and responsible for the progression of Parkinson’s pathology. Moreover, the involvement of the inflammatory response in PD pathogenesis has been reported on the excessive microglial activation and production of pro-inflammatory cytokines. At last, we describe several treatment approaches that target the pathogenic α-syn protein, especially the oligomers, which are currently being tested in advanced animal experiments or are already in clinical trials. However, there are current challenges with therapies that target α-syn, for example, difficulties in identifying varying α-syn conformations within different individuals as well as both the cost and need of long-duration large trials. Frontiers Media S.A. 2018-11-22 /pmc/articles/PMC6261981/ /pubmed/30524265 http://dx.doi.org/10.3389/fnagi.2018.00370 Text en Copyright © 2018 Zhang, Xia, Wan, Ma, Guo, Kou, Yin, Han, Liu, Huang, Xiong and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Zhang, Guoxin
Xia, Yun
Wan, Fang
Ma, Kai
Guo, Xingfang
Kou, Liang
Yin, Sijia
Han, Chao
Liu, Ling
Huang, Jinsha
Xiong, Nian
Wang, Tao
New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
title New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
title_full New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
title_fullStr New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
title_full_unstemmed New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
title_short New Perspectives on Roles of Alpha-Synuclein in Parkinson’s Disease
title_sort new perspectives on roles of alpha-synuclein in parkinson’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6261981/
https://www.ncbi.nlm.nih.gov/pubmed/30524265
http://dx.doi.org/10.3389/fnagi.2018.00370
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