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- W3197441209 abstract "Intercellular propagation of aggregated protein inclusions along actin-based tunneling nanotubes (TNTs) has been reported as a means of pathogenic spread in Alzheimer's, Parkinson's, and Huntington's diseases. Propagation of oligomeric-structured polyglutamine-expanded ataxin-1 (Atxn1[154Q]) has been reported in the cerebellum of a Spinocerebellar ataxia type 1 (SCA1) knock-in mouse to correlate with disease propagation. In this study, we investigated whether a physiologically relevant polyglutamine-expanded ATXN1 protein (ATXN1[82Q]) could propagate intercellularly. Using a cerebellar-derived live cell model, we observed ATXN1 aggregates form in the nucleus, subsequently form in the cytoplasm, and finally, propagate to neighboring cells along actin-based intercellular connections. Additionally, we observed the facilitation of aggregate-resistant proteins into aggregates given the presence of aggregation-prone proteins within cells. Taken together, our results support a pathogenic role of intercellular propagation of polyglutamine-expanded ATXN1 inclusions." @default.
- W3197441209 created "2021-09-13" @default.
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- W3197441209 date "2021-11-26" @default.
- W3197441209 modified "2023-09-26" @default.
- W3197441209 title "Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1" @default.
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- W3197441209 doi "https://doi.org/10.1007/s12031-021-01944-1" @default.
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