The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction

Abstract Huntington’s disease (HD) is a devastating neurodegenerative disorder, caused by a CAG/polyglutamine repeat expansion, that results in the aggregation of the huntingtin protein, culminating in the deposition of inclusion bodies in HD patient brains. We have previously shown that the heat sh...

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Autores principales:	Casandra Gomez-Paredes, Michael A. Mason, Bridget A. Taxy, Aikaterini S. Papadopoulou, Paolo Paganetti, Gillian P. Bates
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4d49ced2d0743ada535353ffd2d0f3e
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spelling	oai:doaj.org-article:c4d49ced2d0743ada535353ffd2d0f3e2021-12-02T16:55:34ZThe heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction10.1038/s41598-021-88715-52045-2322https://doaj.org/article/c4d49ced2d0743ada535353ffd2d0f3e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88715-5https://doaj.org/toc/2045-2322Abstract Huntington’s disease (HD) is a devastating neurodegenerative disorder, caused by a CAG/polyglutamine repeat expansion, that results in the aggregation of the huntingtin protein, culminating in the deposition of inclusion bodies in HD patient brains. We have previously shown that the heat shock response becomes impaired with disease progression in mouse models of HD. The disruption of this inducible arm of the proteostasis network is likely to exacerbate the pathogenesis of this protein-folding disease. To allow a rapid and more comprehensive analysis of the heat shock response, we have developed, and validated, a 16-plex QuantiGene assay that allows the expression of Hsf1 and nine heat shock genes, to be measured directly, and simultaneously, from mouse tissue. We used this QuantiGene assay to show that, following pharmacological activation in vivo, the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. In contrast, although a heat shock impairment could be detected in R6/2 cortex, this was not apparent in the cortex from zQ175 mice. Whilst the mechanism underlying this impairment remains unknown, our data indicated that it is not caused by a reduction in HSF1 levels, as had been reported.Casandra Gomez-ParedesMichael A. MasonBridget A. TaxyAikaterini S. PapadopoulouPaolo PaganettiGillian P. BatesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Casandra Gomez-Paredes Michael A. Mason Bridget A. Taxy Aikaterini S. Papadopoulou Paolo Paganetti Gillian P. Bates The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction
description	Abstract Huntington’s disease (HD) is a devastating neurodegenerative disorder, caused by a CAG/polyglutamine repeat expansion, that results in the aggregation of the huntingtin protein, culminating in the deposition of inclusion bodies in HD patient brains. We have previously shown that the heat shock response becomes impaired with disease progression in mouse models of HD. The disruption of this inducible arm of the proteostasis network is likely to exacerbate the pathogenesis of this protein-folding disease. To allow a rapid and more comprehensive analysis of the heat shock response, we have developed, and validated, a 16-plex QuantiGene assay that allows the expression of Hsf1 and nine heat shock genes, to be measured directly, and simultaneously, from mouse tissue. We used this QuantiGene assay to show that, following pharmacological activation in vivo, the heat shock response impairment in tibialis anterior, brain hemispheres and striatum was comparable between zQ175 and R6/2 mice. In contrast, although a heat shock impairment could be detected in R6/2 cortex, this was not apparent in the cortex from zQ175 mice. Whilst the mechanism underlying this impairment remains unknown, our data indicated that it is not caused by a reduction in HSF1 levels, as had been reported.
format	article
author	Casandra Gomez-Paredes Michael A. Mason Bridget A. Taxy Aikaterini S. Papadopoulou Paolo Paganetti Gillian P. Bates
author_facet	Casandra Gomez-Paredes Michael A. Mason Bridget A. Taxy Aikaterini S. Papadopoulou Paolo Paganetti Gillian P. Bates
author_sort	Casandra Gomez-Paredes
title	The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction
title_short	The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction
title_full	The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction
title_fullStr	The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction
title_full_unstemmed	The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction
title_sort	heat shock response, determined by quantigene multiplex, is impaired in hd mouse models and not caused by hsf1 reduction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c4d49ced2d0743ada535353ffd2d0f3e
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The heat shock response, determined by QuantiGene multiplex, is impaired in HD mouse models and not caused by HSF1 reduction

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