AI Article Synopsis
- This study explores how aggregated forms of the protein ATXN1, linked to spinocerebellar ataxia type 1, spread from one cell to another through tunneling nanotubes.
- Using a live cell model derived from the cerebellum, researchers found that ATXN1 aggregates first appear in the nucleus, then in the cytoplasm, and ultimately move to adjacent cells.
- The findings indicate that the presence of aggregation-prone proteins can facilitate the formation of protein aggregates in neighboring cells, highlighting a potential mechanism for disease progression in related neurodegenerative disorders.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986690 | PMC |
| http://dx.doi.org/10.1007/s12031-021-01944-1 | DOI Listing |
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