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Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1.
- Source :
-
Journal of molecular neuroscience : MN [J Mol Neurosci] 2022 Apr; Vol. 72 (4), pp. 708-718. Date of Electronic Publication: 2021 Nov 26. - Publication Year :
- 2022
-
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.<br /> (© 2021. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1559-1166
- Volume :
- 72
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of molecular neuroscience : MN
- Publication Type :
- Academic Journal
- Accession number :
- 34826062
- Full Text :
- https://doi.org/10.1007/s12031-021-01944-1