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Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders

Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer's disease. They are progressive conditions...

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Autores principales: Manzanza, Nelson de Oliveira, Sedlackova, Lucia, Kalaria, Raj N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267936/
https://www.ncbi.nlm.nih.gov/pubmed/34248606
http://dx.doi.org/10.3389/fnagi.2021.690293
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author Manzanza, Nelson de Oliveira
Sedlackova, Lucia
Kalaria, Raj N.
author_facet Manzanza, Nelson de Oliveira
Sedlackova, Lucia
Kalaria, Raj N.
author_sort Manzanza, Nelson de Oliveira
collection PubMed
description Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer's disease. They are progressive conditions with variable clinical symptoms embodied within specific cognitive and behavioral disorders. There are currently no effective treatments for LBDs. LBDs are histopathologically characterized by the presence of abnormal neuronal inclusions commonly known as Lewy Bodies (LBs) and extracellular Lewy Neurites (LNs). The inclusions predominantly comprise aggregates of alpha-synuclein (aSyn). It has been proposed that post-translational modifications (PTMs) such as aSyn phosphorylation, ubiquitination SUMOylation, Nitration, o-GlcNacylation, and Truncation play important roles in the formation of toxic forms of the protein, which consequently facilitates the formation of these inclusions. This review focuses on the role of different PTMs in aSyn in the pathogenesis of LBDs. We highlight how these PTMs interact with aSyn to promote misfolding and aggregation and interplay with cell membranes leading to the potential functional and pathogenic consequences detected so far, and their involvement in the development of LBDs.
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spelling pubmed-82679362021-07-10 Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders Manzanza, Nelson de Oliveira Sedlackova, Lucia Kalaria, Raj N. Front Aging Neurosci Neuroscience Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer's disease. They are progressive conditions with variable clinical symptoms embodied within specific cognitive and behavioral disorders. There are currently no effective treatments for LBDs. LBDs are histopathologically characterized by the presence of abnormal neuronal inclusions commonly known as Lewy Bodies (LBs) and extracellular Lewy Neurites (LNs). The inclusions predominantly comprise aggregates of alpha-synuclein (aSyn). It has been proposed that post-translational modifications (PTMs) such as aSyn phosphorylation, ubiquitination SUMOylation, Nitration, o-GlcNacylation, and Truncation play important roles in the formation of toxic forms of the protein, which consequently facilitates the formation of these inclusions. This review focuses on the role of different PTMs in aSyn in the pathogenesis of LBDs. We highlight how these PTMs interact with aSyn to promote misfolding and aggregation and interplay with cell membranes leading to the potential functional and pathogenic consequences detected so far, and their involvement in the development of LBDs. Frontiers Media S.A. 2021-06-25 /pmc/articles/PMC8267936/ /pubmed/34248606 http://dx.doi.org/10.3389/fnagi.2021.690293 Text en Copyright © 2021 Manzanza, Sedlackova and Kalaria. https://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
Manzanza, Nelson de Oliveira
Sedlackova, Lucia
Kalaria, Raj N.
Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
title Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
title_full Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
title_fullStr Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
title_full_unstemmed Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
title_short Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders
title_sort alpha-synuclein post-translational modifications: implications for pathogenesis of lewy body disorders
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267936/
https://www.ncbi.nlm.nih.gov/pubmed/34248606
http://dx.doi.org/10.3389/fnagi.2021.690293
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