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• W2132357350 endingPage "1361" @default.
• W2132357350 startingPage "1355" @default.
• W2132357350 abstract "To gain insight into the pathogenic mechanisms of Huntington's disease (HD), we have developed a stable cellular model, using a neuroblastoma cell line in which the expression of full-length or truncated forms of wild-type and mutant huntingtin can be induced. While the wild-type forms have the expected cytoplasmic localization, the expression of mutant proteins leads to the formation of cytoplasmic and nuclear inclusions in a time- and polyglutamine length-dependent manner. The inclusions are ubiquitinated, appear more rapidly in cells expressing truncated forms of mutant huntingtin and are correlated with enhanced apoptosis. In lines expressing mutant full-length huntingtin, major characteristics present in Huntington's patients could be modelled. Selective processing of the mutant, but not the wild-type, full-length huntingtin was observed at late time points, with appearance of a breakdown product corresponding to a predicted caspase-3 cleavage product. A more truncated N-terminal fragment of huntingtin is also produced, that appears involved in building up cytoplasmic inclusions at early time points, and later on also nuclear inclusions. This fits with the finding that inclusions in the brain of HD patients are detected only using antibodies directed against epitopes very close to the polyglutamine stretch. This unique model should thus be useful to study the processing mechanism of mutant huntingtin, its role in the formation of intracellular aggregates and the effect of the latter on cellular physiology." @default.
• W2132357350 created "2016-06-24" @default.
• W2132357350 creator A5008263445 @default.
• W2132357350 creator A5009591144 @default.
• W2132357350 date "1998-09-01" @default.
• W2132357350 modified "2023-09-25" @default.
• W2132357350 title "A cellular model that recapitulates major pathogenic steps of Huntington's disease" @default.
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• W2132357350 doi "https://doi.org/10.1093/hmg/7.9.1355" @default.
• W2132357350 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9700187" @default.
• W2132357350 hasPublicationYear "1998" @default.
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