Analysis of mutant and total huntingtin expression in Huntington’s disease murine models

Abstract Huntington’s disease (HD) is a monogenetic neurodegenerative disorder that is caused by the expansion of a polyglutamine region within the huntingtin (HTT) protein, but there is still an incomplete understanding of the molecular mechanisms that drive pathology. Expression of the mutant form...

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Autores principales:	Valentina Fodale, Roberta Pintauro, Manuel Daldin, Roberta Altobelli, Maria Carolina Spiezia, Monica Bisbocci, Douglas Macdonald, Alberto Bresciani
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f0f9716e3bb54bde98e7f84e35b5a6f0
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spelling	oai:doaj.org-article:f0f9716e3bb54bde98e7f84e35b5a6f02021-12-02T13:34:00ZAnalysis of mutant and total huntingtin expression in Huntington’s disease murine models10.1038/s41598-020-78790-52045-2322https://doaj.org/article/f0f9716e3bb54bde98e7f84e35b5a6f02020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78790-5https://doaj.org/toc/2045-2322Abstract Huntington’s disease (HD) is a monogenetic neurodegenerative disorder that is caused by the expansion of a polyglutamine region within the huntingtin (HTT) protein, but there is still an incomplete understanding of the molecular mechanisms that drive pathology. Expression of the mutant form of HTT is a key aspect of diseased tissues, and the most promising therapeutic approaches aim to lower expanded HTT levels. Consequently, the investigation of HTT expression in time and in multiple tissues, with assays that accurately quantify expanded and non-expanded HTT, are required to delineate HTT homeostasis and to best design and interpret pharmacodynamic readouts for HTT lowering therapeutics. Here we evaluate mutant polyglutamine-expanded (mHTT) and polyglutamine-independent HTT specific immunoassays for validation in human HD and control fibroblasts and use to elucidate the CSF/brain and peripheral tissue expression of HTT in preclinical HD models.Valentina FodaleRoberta PintauroManuel DaldinRoberta AltobelliMaria Carolina SpieziaMonica BisbocciDouglas MacdonaldAlberto BrescianiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valentina Fodale Roberta Pintauro Manuel Daldin Roberta Altobelli Maria Carolina Spiezia Monica Bisbocci Douglas Macdonald Alberto Bresciani Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
description	Abstract Huntington’s disease (HD) is a monogenetic neurodegenerative disorder that is caused by the expansion of a polyglutamine region within the huntingtin (HTT) protein, but there is still an incomplete understanding of the molecular mechanisms that drive pathology. Expression of the mutant form of HTT is a key aspect of diseased tissues, and the most promising therapeutic approaches aim to lower expanded HTT levels. Consequently, the investigation of HTT expression in time and in multiple tissues, with assays that accurately quantify expanded and non-expanded HTT, are required to delineate HTT homeostasis and to best design and interpret pharmacodynamic readouts for HTT lowering therapeutics. Here we evaluate mutant polyglutamine-expanded (mHTT) and polyglutamine-independent HTT specific immunoassays for validation in human HD and control fibroblasts and use to elucidate the CSF/brain and peripheral tissue expression of HTT in preclinical HD models.
format	article
author	Valentina Fodale Roberta Pintauro Manuel Daldin Roberta Altobelli Maria Carolina Spiezia Monica Bisbocci Douglas Macdonald Alberto Bresciani
author_facet	Valentina Fodale Roberta Pintauro Manuel Daldin Roberta Altobelli Maria Carolina Spiezia Monica Bisbocci Douglas Macdonald Alberto Bresciani
author_sort	Valentina Fodale
title	Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
title_short	Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
title_full	Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
title_fullStr	Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
title_full_unstemmed	Analysis of mutant and total huntingtin expression in Huntington’s disease murine models
title_sort	analysis of mutant and total huntingtin expression in huntington’s disease murine models
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/f0f9716e3bb54bde98e7f84e35b5a6f0
work_keys_str_mv	AT valentinafodale analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT robertapintauro analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT manueldaldin analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT robertaaltobelli analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT mariacarolinaspiezia analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT monicabisbocci analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT douglasmacdonald analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels AT albertobresciani analysisofmutantandtotalhuntingtinexpressioninhuntingtonsdiseasemurinemodels
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Analysis of mutant and total huntingtin expression in Huntington’s disease murine models

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