ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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130 citing papers in PubMed, 215 citations in OpenAlex.
- Monovalent Nondegrading Molecular Glues: An Updated Overview of Emerging Mechanisms and Therapeutic Development.Pharmaceuticals (Basel, Switzerland) · 2026Review
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- Experimental Models to Study Polyglutamine Spinocerebellar Ataxias: From Mechanisms to Therapeutic Developments.Cerebellum (London, England) · 2026Review
- Article
- Resilience to Endoplasmic Reticulum Stress Mitigates Membrane Hyperexcitability Underlying Late Disease Onset in a Murine Model of SCA6.Annals of neurology · 2026Article
- Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular hallmarks of neurodegeneration in polyglutamine spinocerebellar ataxias.Cell death & disease · 2025Review
- Nonsteroidal Anti-Inflammatory Drugs as Modulators of Cation Channels: Fenamates Repurposing in Channelopathies.ChemMedChem · 2025Review
- Gene editing for Spinocerebellar ataxia type 3 taking advantage of the human ATXN3L paralog as replacement gene.Gene therapy · 2025Article
- Longitudinal Study and Characterization of Gait Impairment in a Mouse Model of SCA1.Cerebellum (London, England) · 2025Article
- A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait.Experimental animals · 2025Article
- Axonal pathology differentially affects human Purkinje cell subpopulations in the essential tremor cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tsc1 deletion in Purkinje neurons disrupts the axon initial segment, impairing excitability and cerebellar function.Neurobiology of disease · 2025Article
- Axonal pathology differentially affects human Purkinje cell subtypes in the essential tremor cerebellum.bioRxiv : the preprint server for biology · 2025Article
- 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
- Memory decline, anxiety and depression in the mouse model of spinocerebellar ataxia type 3.Human molecular genetics · 2024Article
- Therapeutic role of voltage-gated potassium channels in age-related neurodegenerative diseases.Frontiers in cellular neuroscience · 2024Review
- KJournal of neuroscience research · 2023Review
- Development and validation of an ultrahigh-performance liquid chromatography-tandem mass spectrometry method to investigate the plasma pharmacokinetics of a KRapid communications in mass spectrometry : RCM · 2023Article
70 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The relationship between cerebellar dysfunction, motor symptoms, and neuronal loss in the inherited ataxias, including the polyglutamine disease spinocerebellar ataxia type 3 (SCA3), remains poorly understood. We demonstrate that before neurodegeneration, Purkinje neurons in a mouse model of SCA3 exhibit increased intrinsic excitability resulting in depolarization block and the loss of the ability to sustain spontaneous repetitive firing. These alterations in intrinsic firing are associated with increased inactivation of voltage-activated potassium currents. Administration of an activator of calcium-activated potassium channels, SKA-31, partially corrects abnormal Purkinje cell firing and improves motor function in SCA3 mice. Finally, expression of the disease protein, ataxin-3, in transfected cells increases the inactivation of Kv3.1 channels and shifts the activation of Kv1.2 channels to more depolarized potentials. Our results suggest that in SCA3, early Purkinje neuron dysfunction is associated with altered physiology of voltage-activated potassium channels. We further suggest that the observed changes in Purkinje neuron physiology contribute to disease pathogenesis, underlie at least some motor symptoms, and represent a promising therapeutic target in SCA3.
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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.