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The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias
Polyglutamine (polyQ) spinocerebellar ataxias (SCAs) are the most prevalent subset of SCAs and share the aberrant expansion of Q-encoding CAG repeats within the coding sequences of disease-responsible genes as their common genetic cause. These polyQ SCAs (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) are...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289180/ https://www.ncbi.nlm.nih.gov/pubmed/32581673 http://dx.doi.org/10.3389/fnins.2020.00489 |
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author | Lee, Davin Lee, Yun-Il Lee, Young-Sam Lee, Sung Bae |
author_facet | Lee, Davin Lee, Yun-Il Lee, Young-Sam Lee, Sung Bae |
author_sort | Lee, Davin |
collection | PubMed |
description | Polyglutamine (polyQ) spinocerebellar ataxias (SCAs) are the most prevalent subset of SCAs and share the aberrant expansion of Q-encoding CAG repeats within the coding sequences of disease-responsible genes as their common genetic cause. These polyQ SCAs (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) are inherited neurodegenerative diseases characterized by the progressive atrophy of the cerebellum and connected regions of the nervous system, which leads to loss of fine muscle movement coordination. Upon the expansion of polyQ repeats, the mutated proteins typically accumulate disproportionately in the neuronal nucleus, where they sequester various target molecules, including transcription factors and other nuclear proteins. However, it is not yet clearly understood how CAG repeat expansion takes place or how expanded polyQ proteins accumulate in the nucleus. In this article, we review the current knowledge on the molecular and cellular bases of nuclear proteotoxicity of polyQ proteins in SCAs and present our perspectives on the remaining issues surrounding these diseases. |
format | Online Article Text |
id | pubmed-7289180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72891802020-06-23 The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias Lee, Davin Lee, Yun-Il Lee, Young-Sam Lee, Sung Bae Front Neurosci Neuroscience Polyglutamine (polyQ) spinocerebellar ataxias (SCAs) are the most prevalent subset of SCAs and share the aberrant expansion of Q-encoding CAG repeats within the coding sequences of disease-responsible genes as their common genetic cause. These polyQ SCAs (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) are inherited neurodegenerative diseases characterized by the progressive atrophy of the cerebellum and connected regions of the nervous system, which leads to loss of fine muscle movement coordination. Upon the expansion of polyQ repeats, the mutated proteins typically accumulate disproportionately in the neuronal nucleus, where they sequester various target molecules, including transcription factors and other nuclear proteins. However, it is not yet clearly understood how CAG repeat expansion takes place or how expanded polyQ proteins accumulate in the nucleus. In this article, we review the current knowledge on the molecular and cellular bases of nuclear proteotoxicity of polyQ proteins in SCAs and present our perspectives on the remaining issues surrounding these diseases. Frontiers Media S.A. 2020-06-04 /pmc/articles/PMC7289180/ /pubmed/32581673 http://dx.doi.org/10.3389/fnins.2020.00489 Text en Copyright © 2020 Lee, Lee, Lee and Lee. 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) 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 Lee, Davin Lee, Yun-Il Lee, Young-Sam Lee, Sung Bae The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias |
title | The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias |
title_full | The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias |
title_fullStr | The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias |
title_full_unstemmed | The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias |
title_short | The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias |
title_sort | mechanisms of nuclear proteotoxicity in polyglutamine spinocerebellar ataxias |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289180/ https://www.ncbi.nlm.nih.gov/pubmed/32581673 http://dx.doi.org/10.3389/fnins.2020.00489 |
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