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Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation

Alpha-synuclein (α-syn) is a small protein composed of 140 amino acids and belongs to the group of intrinsically disordered proteins. It is a soluble protein that is highly expressed in neurons and expressed at low levels in glial cells. The monomeric protein aggregation process induces the formatio...

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Autores principales: Chavarría, Cecilia, Ivagnes, Rodrigo, Souza, José M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138387/
https://www.ncbi.nlm.nih.gov/pubmed/35625583
http://dx.doi.org/10.3390/biom12050655
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author Chavarría, Cecilia
Ivagnes, Rodrigo
Souza, José M.
author_facet Chavarría, Cecilia
Ivagnes, Rodrigo
Souza, José M.
author_sort Chavarría, Cecilia
collection PubMed
description Alpha-synuclein (α-syn) is a small protein composed of 140 amino acids and belongs to the group of intrinsically disordered proteins. It is a soluble protein that is highly expressed in neurons and expressed at low levels in glial cells. The monomeric protein aggregation process induces the formation of oligomeric intermediates and proceeds towards fibrillar species. These α-syn conformational species have been detected in the extracellular space and mediate consequences on surrounding neurons and glial cells. In particular, higher-ordered α-syn aggregates are involved in microglial and oligodendrocyte activation, as well as in the induction of astrogliosis. These phenomena lead to mitochondrial dysfunction, reactive oxygen and nitrogen species formation, and the induction of an inflammatory response, associated with neuronal cell death. Several receptors participate in cell activation and/or in the uptake of α-syn, which can vary depending on the α-syn aggregated state and cell types. The receptors involved in this process are of outstanding relevance because they may constitute potential therapeutic targets for the treatment of PD and related synucleinopathies. This review article focuses on the mechanism associated with extracellular α-syn uptake in glial cells and the consequent glial cell activation that contributes to the neuronal death associated with synucleinopathies.
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spelling pubmed-91383872022-05-28 Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation Chavarría, Cecilia Ivagnes, Rodrigo Souza, José M. Biomolecules Review Alpha-synuclein (α-syn) is a small protein composed of 140 amino acids and belongs to the group of intrinsically disordered proteins. It is a soluble protein that is highly expressed in neurons and expressed at low levels in glial cells. The monomeric protein aggregation process induces the formation of oligomeric intermediates and proceeds towards fibrillar species. These α-syn conformational species have been detected in the extracellular space and mediate consequences on surrounding neurons and glial cells. In particular, higher-ordered α-syn aggregates are involved in microglial and oligodendrocyte activation, as well as in the induction of astrogliosis. These phenomena lead to mitochondrial dysfunction, reactive oxygen and nitrogen species formation, and the induction of an inflammatory response, associated with neuronal cell death. Several receptors participate in cell activation and/or in the uptake of α-syn, which can vary depending on the α-syn aggregated state and cell types. The receptors involved in this process are of outstanding relevance because they may constitute potential therapeutic targets for the treatment of PD and related synucleinopathies. This review article focuses on the mechanism associated with extracellular α-syn uptake in glial cells and the consequent glial cell activation that contributes to the neuronal death associated with synucleinopathies. MDPI 2022-04-30 /pmc/articles/PMC9138387/ /pubmed/35625583 http://dx.doi.org/10.3390/biom12050655 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chavarría, Cecilia
Ivagnes, Rodrigo
Souza, José M.
Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation
title Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation
title_full Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation
title_fullStr Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation
title_full_unstemmed Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation
title_short Extracellular Alpha-Synuclein: Mechanisms for Glial Cell Internalization and Activation
title_sort extracellular alpha-synuclein: mechanisms for glial cell internalization and activation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138387/
https://www.ncbi.nlm.nih.gov/pubmed/35625583
http://dx.doi.org/10.3390/biom12050655
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