Progressive degeneration in a new Drosophila model of Spinocerebellar Ataxia type 7.

Autor:	Sujkowski AL; Department of Pharmacology, Wayne State University School of Medicine., Ranxhi B; Department of Pharmacology, Wayne State University School of Medicine., Prifti MV; Department of Pharmacology, Wayne State University School of Medicine., Alam N; Department of Pharmacology, Wayne State University School of Medicine., Todi SV; Department of Pharmacology, Wayne State University School of Medicine.; Department of Neurology, Wayne State University School of Medicine., Tsou WL; Department of Pharmacology, Wayne State University School of Medicine.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2023 Nov 23. Date of Electronic Publication: 2023 Nov 23.
DOI:	10.21203/rs.3.rs-3592641/v1
Abstrakt:	Spinocerebellar ataxia type 7 (SCA7) is a progressive neurodegenerative disorder resulting from abnormal expansion of polyglutamine (polyQ) in its disease protein, ataxin-7 (ATXN7). ATXN7 is part of Spt-Ada-Gcn5 acetyltransferase (SAGA), an evolutionarily conserved transcriptional coactivation complex with critical roles in chromatin remodeling, cell signaling, neurodifferentiation, mitochondrial health and autophagy. SCA7 is dominantly inherited and characterized by genetic anticipation and high repeat-length instability. Patients with SCA7 experience progressive ataxia, atrophy, spasticity, and blindness. There is currently no cure for SCA7, and therapies are aimed at alleviating symptoms to increase quality of life. Here, we report novel Drosophila lines of SCA7 with polyQ repeats in wild-type and human disease patient range. We find that ATXN7 expression has age- and polyQ repeat length-dependent reduction in survival and retinal instability, concomitant with increased ATXN7 protein aggregation. These new lines will provide important insight on disease progression that can be used in the future to identify therapeutic targets for SCA7 patients. Competing Interests: Competing Interests Statement The authors declare that they do not have any conflicts of interest to disclose.
Databáze:	MEDLINE
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