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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...

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Autores principales: Lee, Davin, Lee, Yun-Il, Lee, Young-Sam, Lee, Sung Bae
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
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.
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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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