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Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases

Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ) diseases, are a broad class of neurological disorders. These diseases are characterized by neuronal dysfunction and death, and by the accumulation of toxic aggregation-prone proteins in the forms of inclusions and micro-agg...

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Autores principales: Sambataro, Fabio, Pennuto, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374214/
https://www.ncbi.nlm.nih.gov/pubmed/28408866
http://dx.doi.org/10.3389/fnmol.2017.00082
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author Sambataro, Fabio
Pennuto, Maria
author_facet Sambataro, Fabio
Pennuto, Maria
author_sort Sambataro, Fabio
collection PubMed
description Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ) diseases, are a broad class of neurological disorders. These diseases are characterized by neuronal dysfunction and death, and by the accumulation of toxic aggregation-prone proteins in the forms of inclusions and micro-aggregates. Protein quality control is a cellular mechanism to reduce the burden of accumulation of misfolded proteins, a function that results from the coordinated actions of chaperones and degradation systems, such as the ubiquitin-proteasome system (UPS) and autophagy-lysosomal degradation system. The rate of turnover, aggregation and degradation of the disease-causing proteins is modulated by post-translational modifications (PTMs), such as phosphorylation, arginine methylation, palmitoylation, acetylation, SUMOylation, ubiquitination, and proteolytic cleavage. Here, we describe how PTMs of proteins linked to motor neuron and polyQ diseases can either enhance or suppress protein quality control check and protein aggregation and degradation. The identification of molecular strategies targeting these modifications may offer novel avenues for the treatment of these yet incurable diseases.
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spelling pubmed-53742142017-04-13 Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases Sambataro, Fabio Pennuto, Maria Front Mol Neurosci Neuroscience Neurodegenerative diseases, including motor neuron and polyglutamine (polyQ) diseases, are a broad class of neurological disorders. These diseases are characterized by neuronal dysfunction and death, and by the accumulation of toxic aggregation-prone proteins in the forms of inclusions and micro-aggregates. Protein quality control is a cellular mechanism to reduce the burden of accumulation of misfolded proteins, a function that results from the coordinated actions of chaperones and degradation systems, such as the ubiquitin-proteasome system (UPS) and autophagy-lysosomal degradation system. The rate of turnover, aggregation and degradation of the disease-causing proteins is modulated by post-translational modifications (PTMs), such as phosphorylation, arginine methylation, palmitoylation, acetylation, SUMOylation, ubiquitination, and proteolytic cleavage. Here, we describe how PTMs of proteins linked to motor neuron and polyQ diseases can either enhance or suppress protein quality control check and protein aggregation and degradation. The identification of molecular strategies targeting these modifications may offer novel avenues for the treatment of these yet incurable diseases. Frontiers Media S.A. 2017-03-31 /pmc/articles/PMC5374214/ /pubmed/28408866 http://dx.doi.org/10.3389/fnmol.2017.00082 Text en Copyright © 2017 Sambataro and Pennuto. 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) or licensor 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
Sambataro, Fabio
Pennuto, Maria
Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases
title Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases
title_full Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases
title_fullStr Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases
title_full_unstemmed Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases
title_short Post-translational Modifications and Protein Quality Control in Motor Neuron and Polyglutamine Diseases
title_sort post-translational modifications and protein quality control in motor neuron and polyglutamine diseases
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374214/
https://www.ncbi.nlm.nih.gov/pubmed/28408866
http://dx.doi.org/10.3389/fnmol.2017.00082
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