ArticleThe Journal of clinical investigation2018
Mutant ataxin1 disrupts cerebellar development in spinocerebellar ataxia type 1.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- The importance of non-coding RNAs in environmental stress-related developmental brain disorders: A systematic review of evidence associated with exposure to alcohol, anesthetic drugs, nicotine, and viral infections.Neuroscience and biobehavioral reviews · 2021Pooled it
- Purkinje Cell Loss and Changes in Basket Cell Morphology in Essential Tremor and Other Cerebellar Degenerative Diseases: A Postmortem Study of 332 Brains.Cerebellum (London, England) · 2026Article
- Embryonic spinocerebellar ataxia type 37-associated AUUUC repeat RNA causes neurodevelopmental defects.Disease models & mechanisms · 2026Article
- Restoring early postnatal synaptic dysregulation rescues motor neuron degeneration in a mouse model of Spinal and Bulbar Muscular Atrophy.Nature communications · 2026Article
- A conserved differentiation programme facilitates inhibitory neuron production in the developing mouse and human cerebellum.Development (Cambridge, England) · 2025Article
- Disrupted Transcriptional Networks in Mammalian Cells Stably Over-Expressing Pathogenic Atrophin-1.Journal of neuroscience research · 2025Article
- Cerebellar organoids model cell type-specific FOXP2 expression during human cerebellar development.Disease models & mechanisms · 2025Article
- Disrupted Transcriptional Networks by Mutant Atrophin-1 in a Cell Culture Model of Dentatorubral-Pallidoluysian Atrophy.bioRxiv : the preprint server for biology · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias.Cerebellum (London, England) · 2024Review
- Expanded ATXN1 alters transcription and calcium signaling in SCA1 human motor neurons differentiated from induced pluripotent stem cells.Neurobiology of disease · 2024Article
- CAG repeat mosaicism is gene specific in spinocerebellar ataxias.American journal of human genetics · 2024Article
- Longitudinal single-cell transcriptional dynamics throughout neurodegeneration in SCA1.Neuron · 2024Article
- Comparative Transcriptomic Analysis of Cerebellar Astrocytes across Developmental Stages and Brain Regions.International journal of molecular sciences · 2024Article
- Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1.Neuron · 2023Article
- Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway.Journal of neuroinflammation · 2023Article
- Therapeutic Strategies for Spinocerebellar Ataxia Type 1.Biomolecules · 2023Review
- Differential effects of Wnt-β-catenin signaling in Purkinje cells and Bergmann glia in spinocerebellar ataxia type 1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification of the ataxin-1 interaction network and its impact on spinocerebellar ataxia type 1.Human genomics · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Spinocerebellar ataxia type 1 (SCA1) is an adult-onset neurodegenerative disease caused by a polyglutamine expansion in the protein ATXN1, which is involved in transcriptional regulation. Although symptoms appear relatively late in life, primarily from cerebellar dysfunction, pathogenesis begins early, with transcriptional changes detectable as early as a week after birth in SCA1-knockin mice. Given the importance of this postnatal period for cerebellar development, we asked whether this region might be developmentally altered by mutant ATXN1. We found that expanded ATXN1 stimulates the proliferation of postnatal cerebellar stem cells in SCA1 mice. These hyperproliferating stem cells tended to differentiate into GABAergic inhibitory interneurons rather than astrocytes; this significantly increased the GABAergic inhibitory interneuron synaptic connections, disrupting cerebellar Purkinje cell function in a non-cell autonomous manner. We confirmed the increased basket cell-Purkinje cell connectivity in human SCA1 patients. Mutant ATXN1 thus alters the neural circuitry of the developing cerebellum, setting the stage for the later vulnerability of Purkinje cells to SCA1. We propose that other late-onset degenerative diseases may also be rooted in subtle developmental derailments.
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Registered trials
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.