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The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias

Huntington's disease and several of the spinocerebellar ataxias are caused by the abnormal expansion of a CAG repeat within the coding region of the disease gene. This results in the production of a mutant protein with an abnormally expanded polyglutamine tract. Although these disorders have a...

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Autores principales: Davies, Janet E, Sarkar, Sovan, Rubinsztein, David C
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2106366/
https://www.ncbi.nlm.nih.gov/pubmed/18047739
http://dx.doi.org/10.1186/1471-2091-8-S1-S2
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author Davies, Janet E
Sarkar, Sovan
Rubinsztein, David C
author_facet Davies, Janet E
Sarkar, Sovan
Rubinsztein, David C
author_sort Davies, Janet E
collection PubMed
description Huntington's disease and several of the spinocerebellar ataxias are caused by the abnormal expansion of a CAG repeat within the coding region of the disease gene. This results in the production of a mutant protein with an abnormally expanded polyglutamine tract. Although these disorders have a clear monogenic cause, each polyglutamine expansion mutation is likely to cause the dysfunction of many pathways and processes within the cell. It has been proposed that the ubiquitin proteasome system is impaired in polyglutamine expansion disorders and that this contributes to pathology. However, this is controversial with some groups demonstrating decreased proteasome activity in polyglutamine expansion disorders, some showing no change in activity and others demonstrating an increase in proteasome activity. It remains unknown whether the ubiquitin proteasome system is a feasible therapeutic target in these disorders. Here we review the conflicting results obtained from different assays performed in a variety of different systems. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; ).
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spelling pubmed-21063662007-12-05 The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias Davies, Janet E Sarkar, Sovan Rubinsztein, David C BMC Biochem Review Huntington's disease and several of the spinocerebellar ataxias are caused by the abnormal expansion of a CAG repeat within the coding region of the disease gene. This results in the production of a mutant protein with an abnormally expanded polyglutamine tract. Although these disorders have a clear monogenic cause, each polyglutamine expansion mutation is likely to cause the dysfunction of many pathways and processes within the cell. It has been proposed that the ubiquitin proteasome system is impaired in polyglutamine expansion disorders and that this contributes to pathology. However, this is controversial with some groups demonstrating decreased proteasome activity in polyglutamine expansion disorders, some showing no change in activity and others demonstrating an increase in proteasome activity. It remains unknown whether the ubiquitin proteasome system is a feasible therapeutic target in these disorders. Here we review the conflicting results obtained from different assays performed in a variety of different systems. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; ). BioMed Central 2007-11-22 /pmc/articles/PMC2106366/ /pubmed/18047739 http://dx.doi.org/10.1186/1471-2091-8-S1-S2 Text en Copyright © 2007 Davies et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Davies, Janet E
Sarkar, Sovan
Rubinsztein, David C
The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
title The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
title_full The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
title_fullStr The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
title_full_unstemmed The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
title_short The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias
title_sort ubiquitin proteasome system in huntington's disease and the spinocerebellar ataxias
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2106366/
https://www.ncbi.nlm.nih.gov/pubmed/18047739
http://dx.doi.org/10.1186/1471-2091-8-S1-S2
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