ArticleNeurobiology of disease2018
Reduction of protein kinase A-mediated phosphorylation of ATXN1-S776 in Purkinje cells delays onset of Ataxia in a SCA1 mouse model.
Article in Neurobiology of disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Translational Relevance of SCA1 Models for the Development of Therapies for Spinocerebellar Ataxia Type 1.Biomedicines · 2025Review
- Spinocerebellar Ataxia Type 1 (SCA1) Cell Models Display Widespread Mitochondrial and Extra-Nuclear Alterations.Journal of molecular neuroscience : MN · 2025Article
- Roots of Progress: Uncovering Cerebellar Ataxias Using iPSC Models.Biomedicines · 2025Review
- The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.Cerebellum (London, England) · 2024Review
- Widespread alternative splicing dysregulation occurs presymptomatically in CAG expansion spinocerebellar ataxias.Brain : a journal of neurology · 2024Article
- Functional implications of paralog genes in polyglutamine spinocerebellar ataxias.Human genetics · 2023Review
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Article
- Suppressing gain-of-function proteins via CRISPR/Cas9 system in SCA1 cells.Scientific reports · 2022Article
- Identification of the ataxin-1 interaction network and its impact on spinocerebellar ataxia type 1.Human genomics · 2022Article
- Intercellular Propagation and Aggregate Seeding of Mutant Ataxin-1.Journal of molecular neuroscience : MN · 2022Article
- Human Induced Pluripotent Stem Cell-Based Modelling of Spinocerebellar Ataxias.Stem cell reviews and reports · 2022Review
- Patient-Specific iPSCs-Based Models of Neurodegenerative Diseases: Focus on Aberrant Calcium Signaling.International journal of molecular sciences · 2022Review
- Article
- A Structural Study of the Cytoplasmic Chaperone Effect of 14-3-3 Proteins on Ataxin-1.Journal of molecular biology · 2021Article
- New Perspectives of Gene Therapy on Polyglutamine Spinocerebellar Ataxias: From Molecular Targets to Novel Nanovectors.Pharmaceutics · 2021Review
- Modulation of ATXN1 S776 phosphorylation reveals the importance of allele-specific targeting in SCA1.JCI insight · 2021Article
- Ubiquitin signaling in neurodegenerative diseases: an autophagy and proteasome perspective.Cell death and differentiation · 2021Review
- C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside.Current neuropharmacology · 2021Review
- Pathogenic mechanisms underlying spinocerebellar ataxia type 1.Cellular and molecular life sciences : CMLS · 2020Review
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Authors and funding
14 authors at 4 institutions in 1 country.
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Abstract
Spinocerebellar ataxia type 1 (SCA1) is a polyglutamine (polyQ) repeat neurodegenerative disease in which a primary site of pathogenesis are cerebellar Purkinje cells. In addition to polyQ expansion of ataxin-1 protein (ATXN1), phosphorylation of ATXN1 at the serine 776 residue (ATXN1-pS776) plays a significant role in protein toxicity. Utilizing a biochemical approach, pharmacological agents and cell-based assays, including SCA1 patient iPSC-derived neurons, we examine the role of Protein Kinase A (PKA) as an effector of ATXN1-S776 phosphorylation. We further examine the implications of PKA-mediated phosphorylation at ATXN1-S776 on SCA1 through genetic manipulation of the PKA catalytic subunit Cα in Pcp2-ATXN1[82Q] mice. Here we show that pharmacologic inhibition of S776 phosphorylation in transfected cells and SCA1 patient iPSC-derived neuronal cells lead to a decrease in ATXN1. In vivo, reduction of PKA-mediated ATXN1-pS776 results in enhanced degradation of ATXN1 and improved cerebellar-dependent motor performance. These results provide evidence that PKA is a biologically important kinase for ATXN1-pS776 in cerebellar Purkinje cells.
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Registered trials
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