ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Chronic suppression of inositol 1,4,5-triphosphate receptor-mediated calcium signaling in cerebellar purkinje cells alleviates pathological phenotype in spinocerebellar ataxia 2 mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 110 citations in OpenAlex.
- Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia.Brain research bulletin · 2026Article
- Toll-like receptor 4 deficiency in Purkinje neurons drives cerebellar ataxia by impairing the BK channel-mediated after-hyperpolarization and cytosolic calcium homeostasis.Cell death & disease · 2024Article
- A combination of chlorzoxazone and folic acid improves recognition memory, anxiety and depression in SCA3-84Q mice.Human molecular genetics · 2024Article
- The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease.Cell death & disease · 2024Review
- Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.Neurobiology of disease · 2024Article
- Cognitive Decline and Mood Alterations in the Mouse Model of Spinocerebellar Ataxia Type 2.Cerebellum (London, England) · 2024Article
- Early-onset familial essential tremor is associated with nucleotide expansions of spinocerebellar ataxia in China.Molecular biology reports · 2024Article
- Detailed Analysis of ITPR1 Missense Variants Guides Diagnostics and Therapeutic Design.Movement disorders : official journal of the Movement Disorder Society · 2024Article
- A chlorzoxazone-folic acid combination improves cognitive affective decline in SCA2-58Q mice.Scientific reports · 2023Article
- Article
- Review
- Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia.Frontiers in systems neuroscience · 2023Review
- Electrophysiological Studies Support Utility of Positive Modulators of SK Channels for the Treatment of Spinocerebellar Ataxia Type 2.Cerebellum (London, England) · 2022Review
- The Emerging Key Role of the mGluR1-PKCγ Signaling Pathway in the Pathogenesis of Spinocerebellar Ataxias: A Neurodevelopmental Viewpoint.International journal of molecular sciences · 2022Review
- Consensus Paper: Strengths and Weaknesses of Animal Models of Spinocerebellar Ataxias and Their Clinical Implications.Cerebellum (London, England) · 2022Article
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- Review
- Subtype-selective positive modulation of KBritish journal of pharmacology · 2022Article
- Structure-Activity Relationship Study of Subtype-Selective Positive Modulators of KJournal of medicinal chemistry · 2022Article
- Calpain-mediated proteolysis as driver and modulator of polyglutamine toxicity.Frontiers in molecular neuroscience · 2022Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Spinocerebellar ataxia 2 (SCA2) is a neurodegenerative disorder characterized by progressive ataxia. SCA2 results from a poly(Q) (polyglutamine) expansion in the cytosolic protein ataxin-2 (Atx2). Cerebellar Purkinje cells (PCs) are primarily affected in SCA2, but the cause of PC dysfunction and death in SCA2 is poorly understood. In previous studies, we reported that mutant but not wild-type Atx2 specifically binds the inositol 1,4,5-trisphosphate receptor (InsP(3)R) and increases its sensitivity to activation by InsP3. We further proposed that the resulting supranormal calcium (Ca2+) release from the PC endoplasmic reticulum plays a key role in the development of SCA2 pathology. To test this hypothesis, we achieved a chronic suppression of InsP(3)R-mediated Ca2+ signaling by adenoassociated virus-mediated expression of the inositol 1,4,5-phosphatase (Inpp5a) enzyme (5PP) in PCs of a SCA2 transgenic mouse model. We determined that recombinant 5PP overexpression alleviated age-dependent dysfunction in the firing pattern of SCA2 PCs. We further discovered that chronic 5PP overexpression also rescued age-dependent motor incoordination and PC death in SCA2 mice. Our findings further support the important role of supranormal Ca2+ signaling in SCA2 pathogenesis and suggest that partial inhibition of InsP3-mediated Ca2+ signaling could provide therapeutic benefit for the patients afflicted with SCA2 and possibly other SCAs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.