ArticleJournal of Huntington's disease2018
Inhibition of TRPC1-Dependent Store-Operated Calcium Entry Improves Synaptic Stability and Motor Performance in a Mouse Model of Huntington's Disease.
Article in Journal of Huntington's disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- STIM-Orai signaling in neurons: integrating calcium dynamics and synaptic plasticity.Cell communication and signaling : CCS · 2026Review
- Dysregulation of store-operated calcium entry in fibroblast lines from adult and juvenile-onset Huntington's disease patients.Pharmacological reports : PR · 2026Article
- STIM Proteins: The Gas and Brake of Calcium Entry in Neurons.Neuroscience bulletin · 2025Review
- Advancements in CRISPR-Based Therapies for Genetic Modulation in Neurodegenerative Disorders.Current gene therapy · 2025Review
- Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing.Molecular biotechnology · 2024Review
- Recent advancement of sonogenetics: A promising noninvasive cellular manipulation by ultrasound.Genes & diseases · 2024Review
- Calcium channel signalling at neuronal endoplasmic reticulum-plasma membrane junctions.Biochemical Society transactions · 2024Review
- SOCE as a regulator of neuronal activity.The Journal of physiology · 2024Review
- STIM2 regulates NMDA receptor endocytosis that is induced by short-term NMDA receptor overactivation in cortical neurons.Cellular and molecular life sciences : CMLS · 2023Article
- Vector enabled CRISPR gene editing - A revolutionary strategy for targeting the diversity of brain pathologies.Coordination chemistry reviews · 2023Article
- Mitochondria in Huntington's disease: implications in pathogenesis and mitochondrial-targeted therapeutic strategies.Neural regeneration research · 2023Review
- Protocol Optimization for Direct Reprogramming of Primary Human Fibroblast into Induced Striatal Neurons.International journal of molecular sciences · 2023Article
- The mechanosensitive ion channel Piezo1 modulates the migration and immune response of microglia.iScience · 2023Article
- Astrocytes Reduce Store-Operated CaPharmaceuticals (Basel, Switzerland) · 2022Article
- CRISPR/Cas9 gene editing: New hope for Alzheimer's disease therapeutics.Journal of advanced research · 2022Review
- Gene Therapy Approach with an Emphasis on Growth Factors: Theoretical and Clinical Outcomes in Neurodegenerative Diseases.Molecular neurobiology · 2022Review
- STIM and Orai Mediated Regulation of Calcium Signaling in Age-Related Diseases.Frontiers in aging · 2022Review
- Review
- Genetic Screen in Adult Drosophila Reveals That dCBP Depletion in Glial Cells Mitigates Huntington Disease Pathology through a Foxo-Dependent Pathway.International journal of molecular sciences · 2021Article
- Molecular Components of Store-Operated Calcium Channels in the Regulation of Neural Stem Cell Physiology, Neurogenesis, and the Pathology of Huntington's Disease.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundHuntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. We previously discovered that mutant Huntingtin sensitizes type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) to InsP3. This causes calcium leakage from the endoplasmic reticulum (ER) and a compensatory increase in neuronal store-operated calcium (nSOC) entry. We previously demonstrated that supranormal nSOC leads to synaptic loss in striatal medium spiny neurons (MSNs) in YAC128 HD mice.
objectiveWe sought to identify calcium channels supporting supranormal nSOC in HD MSNs and to validate these channels as potential therapeutic targets for HD.
methodsCortico-striatal cultures were established from wild type and YAC128 HD mice and the density of MSN spines was quantified. The expression of candidate nSOC components was suppressed by RNAi knockdown and by CRISPR/Cas9 knockout. TRPC1 knockout mice were crossed with YAC128 HD mice for evaluation of motor performance in a beamwalk assay.
resultsRNAi-mediated knockdown of TRPC1, TRPC6, Orai1, or Orai2, but not other TRPC isoforms or Orai3, rescued the density of YAC128 MSN spines. Knockdown of stromal interaction molecule 1 (STIM1), an ER calcium sensor and nSOC activator, also rescued YAC128 MSN spines. Knockdown of the same targets suppressed supranormal nSOC in YAC128 MSN spines. These channel subunits co-immunoprecipitated with STIM1 and STIM2 in synaptosomal lysates from mouse striata. Crossing YAC128 mice with TRPC1 knockout mice improved motor performance and rescued MSN spines in vitro and in vivo, indicating that inhibition of TRPC1 may serve as a neuroprotective strategy for HD treatment.
conclusionsTRPC1 channels constitute a potential therapeutic target for treatment of HD.
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Registered trials
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