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A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases

The presence and aggregation of misfolded proteins has deleterious effects in the nervous system. Among the various diseases caused by misfolded proteins is the family of the polyglutamine (polyQ) disorders. This family comprises nine members, all stemming from the same mutation—the abnormal elongat...

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Autores principales: Johnson, Sean L., Tsou, Wei-Ling, Prifti, Matthew V., Harris, Autumn L., Todi, Sokol V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515312/
https://www.ncbi.nlm.nih.gov/pubmed/36187346
http://dx.doi.org/10.3389/fnmol.2022.974167
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author Johnson, Sean L.
Tsou, Wei-Ling
Prifti, Matthew V.
Harris, Autumn L.
Todi, Sokol V.
author_facet Johnson, Sean L.
Tsou, Wei-Ling
Prifti, Matthew V.
Harris, Autumn L.
Todi, Sokol V.
author_sort Johnson, Sean L.
collection PubMed
description The presence and aggregation of misfolded proteins has deleterious effects in the nervous system. Among the various diseases caused by misfolded proteins is the family of the polyglutamine (polyQ) disorders. This family comprises nine members, all stemming from the same mutation—the abnormal elongation of a polyQ repeat in nine different proteins—which causes protein misfolding and aggregation, cellular dysfunction and disease. While it is the same type of mutation that causes them, each disease is distinct: it is influenced by regions and domains that surround the polyQ repeat; by proteins with which they interact; and by posttranslational modifications they receive. Here, we overview the role of non-polyQ regions that control the pathogenicity of the expanded polyQ repeat. We begin by introducing each polyQ disease, the genes affected, and the symptoms experienced by patients. Subsequently, we provide a survey of protein-protein interactions and posttranslational modifications that regulate polyQ toxicity. We conclude by discussing shared processes and pathways that bring some of the polyQ diseases together and may serve as common therapeutic entry points for this family of incurable disorders.
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spelling pubmed-95153122022-09-29 A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases Johnson, Sean L. Tsou, Wei-Ling Prifti, Matthew V. Harris, Autumn L. Todi, Sokol V. Front Mol Neurosci Neuroscience The presence and aggregation of misfolded proteins has deleterious effects in the nervous system. Among the various diseases caused by misfolded proteins is the family of the polyglutamine (polyQ) disorders. This family comprises nine members, all stemming from the same mutation—the abnormal elongation of a polyQ repeat in nine different proteins—which causes protein misfolding and aggregation, cellular dysfunction and disease. While it is the same type of mutation that causes them, each disease is distinct: it is influenced by regions and domains that surround the polyQ repeat; by proteins with which they interact; and by posttranslational modifications they receive. Here, we overview the role of non-polyQ regions that control the pathogenicity of the expanded polyQ repeat. We begin by introducing each polyQ disease, the genes affected, and the symptoms experienced by patients. Subsequently, we provide a survey of protein-protein interactions and posttranslational modifications that regulate polyQ toxicity. We conclude by discussing shared processes and pathways that bring some of the polyQ diseases together and may serve as common therapeutic entry points for this family of incurable disorders. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9515312/ /pubmed/36187346 http://dx.doi.org/10.3389/fnmol.2022.974167 Text en Copyright © 2022 Johnson, Tsou, Prifti, Harris and Todi. 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
Johnson, Sean L.
Tsou, Wei-Ling
Prifti, Matthew V.
Harris, Autumn L.
Todi, Sokol V.
A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
title A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
title_full A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
title_fullStr A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
title_full_unstemmed A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
title_short A survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
title_sort survey of protein interactions and posttranslational modifications that influence the polyglutamine diseases
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515312/
https://www.ncbi.nlm.nih.gov/pubmed/36187346
http://dx.doi.org/10.3389/fnmol.2022.974167
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