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Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein

In a number of neurological diseases including Parkinson’s disease (PD), α‑synuclein is aberrantly folded, forming abnormal oligomers, and amyloid fibrils within nerve cells. Strong evidence exists for the toxicity of increased production and aggregation of α-synuclein in vivo. The toxicity of α-syn...

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Autores principales: Roberts, Hazel L., Brown, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496673/
https://www.ncbi.nlm.nih.gov/pubmed/25816357
http://dx.doi.org/10.3390/biom5020282
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author Roberts, Hazel L.
Brown, David R.
author_facet Roberts, Hazel L.
Brown, David R.
author_sort Roberts, Hazel L.
collection PubMed
description In a number of neurological diseases including Parkinson’s disease (PD), α‑synuclein is aberrantly folded, forming abnormal oligomers, and amyloid fibrils within nerve cells. Strong evidence exists for the toxicity of increased production and aggregation of α-synuclein in vivo. The toxicity of α-synuclein is popularly attributed to the formation of “toxic oligomers”: a heterogenous and poorly characterized group of conformers that may share common molecular features. This review presents the available evidence on the properties of α-synuclein oligomers and the potential molecular mechanisms of their cellular disruption. Toxic α-synuclein oligomers may impact cells in a number of ways, including the disruption of membranes, mitochondrial depolarization, cytoskeleton changes, impairment of protein clearance pathways, and enhanced oxidative stress. We also examine the relationship between α-synuclein toxic oligomers and amyloid fibrils, in the light of recent studies that paint a more complex picture of α-synuclein toxicity. Finally, methods of studying and manipulating oligomers within cells are described.
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spelling pubmed-44966732015-07-10 Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein Roberts, Hazel L. Brown, David R. Biomolecules Review In a number of neurological diseases including Parkinson’s disease (PD), α‑synuclein is aberrantly folded, forming abnormal oligomers, and amyloid fibrils within nerve cells. Strong evidence exists for the toxicity of increased production and aggregation of α-synuclein in vivo. The toxicity of α-synuclein is popularly attributed to the formation of “toxic oligomers”: a heterogenous and poorly characterized group of conformers that may share common molecular features. This review presents the available evidence on the properties of α-synuclein oligomers and the potential molecular mechanisms of their cellular disruption. Toxic α-synuclein oligomers may impact cells in a number of ways, including the disruption of membranes, mitochondrial depolarization, cytoskeleton changes, impairment of protein clearance pathways, and enhanced oxidative stress. We also examine the relationship between α-synuclein toxic oligomers and amyloid fibrils, in the light of recent studies that paint a more complex picture of α-synuclein toxicity. Finally, methods of studying and manipulating oligomers within cells are described. MDPI 2015-03-25 /pmc/articles/PMC4496673/ /pubmed/25816357 http://dx.doi.org/10.3390/biom5020282 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Roberts, Hazel L.
Brown, David R.
Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
title Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
title_full Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
title_fullStr Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
title_full_unstemmed Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
title_short Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein
title_sort seeking a mechanism for the toxicity of oligomeric α-synuclein
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496673/
https://www.ncbi.nlm.nih.gov/pubmed/25816357
http://dx.doi.org/10.3390/biom5020282
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