ArticleJournal of molecular neuroscience : MN2012
Differential degradation of full-length and cleaved ataxin-7 fragments in a novel stable inducible SCA7 model.
Article in Journal of molecular neuroscience : MN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Experimental Models to Study Polyglutamine Spinocerebellar Ataxias: From Mechanisms to Therapeutic Developments.Cerebellum (London, England) · 2026Review
- Article
- Key Modulators of the Stress Granule Response TIA1, TDP-43, and G3BP1 Are Altered by Polyglutamine-Expanded ATXN7.Molecular neurobiology · 2022Article
- Altered H3 histone acetylation impairs high-fidelity DNA repair to promote cerebellar degeneration in spinocerebellar ataxia type 7.Cell reports · 2021Article
- Oxidative Stress in DNA Repeat Expansion Disorders: A Focus on NRF2 Signaling Involvement.Biomolecules · 2020Review
- Motor Performances of Spontaneous and Genetically Modified Mutants with Cerebellar Atrophy.Cerebellum (London, England) · 2019Review
- Structural and dynamic studies reveal that the Ala-rich region of ataxin-7 initiates α-helix formation of the polyQ tract but suppresses its aggregation.Scientific reports · 2019Article
- Autophagy in polyglutamine disease: Imposing order on disorder or contributing to the chaos?Molecular and cellular neurosciences · 2015Review
- Consensus paper: pathological mechanisms underlying neurodegeneration in spinocerebellar ataxias.Cerebellum (London, England) · 2014Article
- From pathways to targets: understanding the mechanisms behind polyglutamine disease.BioMed research international · 2014Review
- Inhibition of autophagy via p53-mediated disruption of ULK1 in a SCA7 polyglutamine disease model.Journal of molecular neuroscience : MN · 2013Article
- Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model.BMC neuroscience · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine repeats, and a common toxic gain-of-function mechanism has been proposed. Proteolytic cleavage of several polyglutamine proteins has been identified and suggested to modulate the polyglutamine toxicity. In this study, we show that full-length and cleaved fragments of the SCA7 disease protein ataxin-7 (ATXN7) are differentially degraded. We found that the ubiquitin-proteosome system (UPS) was essential for the degradation of full-length endogenous ATXN7 or transgenic full-length ATXN7 with a normal or expanded glutamine repeat in both HEK 293T and stable PC12 cells. However, a similar contribution by UPS and autophagy was found for the degradation of proteolytically cleaved ATXN7 fragments. Furthermore, in our novel stable inducible PC12 model, induction of mutant ATXN7 expression resulted in toxicity and this toxicity was worsened by inhibition of either UPS or autophagy. In contrast, pharmacological activation of autophagy could ameliorate the ATXN7-induced toxicity. Based on our findings, we propose that both UPS and autophagy are important for the reduction of mutant ataxin-7-induced toxicity, and enhancing ATXN7 clearance through autophagy could be used as a potential therapeutic strategy in SCA7.
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