Normal aging modulates the neurotoxicity of mutant huntingtin.

Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD), a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt), the role of aging is unclear. For a given tract length, the probability of disease onset increases with ag...

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Autores principales:	Elsa Diguet, Fanny Petit, Carole Escartin, Karine Cambon, Nicolas Bizat, Noëlle Dufour, Philippe Hantraye, Nicole Déglon, Emmanuel Brouillet
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05c5333cf7b94ae0824b4acd577e12e4
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spelling	oai:doaj.org-article:05c5333cf7b94ae0824b4acd577e12e42021-11-25T06:17:02ZNormal aging modulates the neurotoxicity of mutant huntingtin.1932-620310.1371/journal.pone.0004637https://doaj.org/article/05c5333cf7b94ae0824b4acd577e12e42009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19247483/?tool=EBIhttps://doaj.org/toc/1932-6203Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD), a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt), the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal) reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week) and old (15 month) rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.Elsa DiguetFanny PetitCarole EscartinKarine CambonNicolas BizatNoëlle DufourPhilippe HantrayeNicole DéglonEmmanuel BrouilletPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4637 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elsa Diguet Fanny Petit Carole Escartin Karine Cambon Nicolas Bizat Noëlle Dufour Philippe Hantraye Nicole Déglon Emmanuel Brouillet Normal aging modulates the neurotoxicity of mutant huntingtin.
description	Aging likely plays a role in neurodegenerative disorders. In Huntington's disease (HD), a disorder caused by an abnormal expansion of a polyglutamine tract in the protein huntingtin (Htt), the role of aging is unclear. For a given tract length, the probability of disease onset increases with age. There are mainly two hypotheses that could explain adult onset in HD: Either mutant Htt progressively produces cumulative defects over time or "normal" aging renders neurons more vulnerable to mutant Htt toxicity. In the present study, we directly explored whether aging affected the toxicity of mutant Htt in vivo. We studied the impact of aging on the effects produced by overexpression of an N-terminal fragment of mutant Htt, of wild-type Htt or of a beta-Galactosidase (beta-Gal) reporter gene in the rat striatum. Stereotaxic injections of lentiviral vectors were performed simultaneously in young (3 week) and old (15 month) rats. Histological evaluation at different time points after infection demonstrated that the expression of mutant Htt led to pathological changes that were more severe in old rats, including an increase in the number of small Htt-containing aggregates in the neuropil, a greater loss of DARPP-32 immunoreactivity and striatal neurons as assessed by unbiased stereological counts.The present results support the hypothesis that "normal" aging is involved in HD pathogenesis, and suggest that age-related cellular defects might constitute potential therapeutic targets for HD.
format	article
author	Elsa Diguet Fanny Petit Carole Escartin Karine Cambon Nicolas Bizat Noëlle Dufour Philippe Hantraye Nicole Déglon Emmanuel Brouillet
author_facet	Elsa Diguet Fanny Petit Carole Escartin Karine Cambon Nicolas Bizat Noëlle Dufour Philippe Hantraye Nicole Déglon Emmanuel Brouillet
author_sort	Elsa Diguet
title	Normal aging modulates the neurotoxicity of mutant huntingtin.
title_short	Normal aging modulates the neurotoxicity of mutant huntingtin.
title_full	Normal aging modulates the neurotoxicity of mutant huntingtin.
title_fullStr	Normal aging modulates the neurotoxicity of mutant huntingtin.
title_full_unstemmed	Normal aging modulates the neurotoxicity of mutant huntingtin.
title_sort	normal aging modulates the neurotoxicity of mutant huntingtin.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/05c5333cf7b94ae0824b4acd577e12e4
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Normal aging modulates the neurotoxicity of mutant huntingtin.

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