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• W2059290723 endingPage "e4637" @default.
• W2059290723 startingPage "e4637" @default.
• W2059290723 abstract "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." @default.
• W2059290723 created "2016-06-24" @default.
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• W2059290723 date "2009-02-27" @default.
• W2059290723 modified "2023-10-18" @default.
• W2059290723 title "Normal Aging Modulates the Neurotoxicity of Mutant Huntingtin" @default.
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• W2059290723 doi "https://doi.org/10.1371/journal.pone.0004637" @default.
• W2059290723 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2645678" @default.
• W2059290723 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19247483" @default.
• W2059290723 hasPublicationYear "2009" @default.
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