ArticleMolecular brain2020
mGluR5 regulates REST/NRSF signaling through N-cadherin/β-catenin complex in Huntington's disease.
Article in Molecular brain, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Hepatocyte BDNF Acts as a Novel Immune Checkpoint to Restrain TLR4-Mediated Acute Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabotropic Glutamate Receptor-Dependent Synaptic Plasticity in Age-Related Neurodegenerative Disorders.Neural plasticity · 2026Review
- Pharmacological inhibition of RE1 silencing transcription factor disrupts SOX2 expression and neurogenesis in human induced pluripotent stem cells derived neuronal models.Metabolic brain disease · 2025Article
- The Dynamic Roles of Repressor Element 1-Silencing Transcription Factor (REST): A Double-Edged Sword in Neural Health and Disease.Molecular neurobiology · 2025Review
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- Neuroprotection by ADAM10 inhibition requires TrkB signaling in the Huntington's disease hippocampus.Cellular and molecular life sciences : CMLS · 2024Article
- Identification of Inhibitors of the Disease-Associated Protein Phosphatase Scp1 Using Antibody Mimetic Molecules.International journal of molecular sciences · 2024Article
- Transplanted human neural stem cells rescue phenotypes in zQ175 Huntington's disease mice and innervate the striatum.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- Repressor Element-1 Binding Transcription Factor (REST) as a Possible Epigenetic Regulator of Neurodegeneration and MicroRNA-Based Therapeutic Strategies.Molecular neurobiology · 2023Review
- Enhancing Endocannabinoid Signaling via β-Catenin in the Nucleus Accumbens Attenuates PTSD- and Depression-like Behavior of Male Rats.Biomedicines · 2022Article
- Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease.Scientific reports · 2022Article
- Insights into Human-Induced Pluripotent Stem Cell-Derived Astrocytes in Neurodegenerative Disorders.Biomolecules · 2022Review
- Metabotropic Glutamate Receptor 5 Antagonism Reduces Pathology and Differentially Improves Symptoms in Male and Female Heterozygous zQ175 Huntington's Mice.Frontiers in molecular neuroscience · 2022Article
- Targeting the Type 5 Metabotropic Glutamate Receptor: A Potential Therapeutic Strategy for Neurodegenerative Diseases?Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 4 countries.
Funding
Abstract
Repressor element 1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a transcription repressor and its expression is regulated by the Wnt pathway through β-catenin. Metabotropic glutamate receptor 5 (mGluR5) signaling plays a key role in controlling neuronal gene expression. Interestingly, REST/NRSF nuclear translocation and signaling, as well as mGluR5 signaling are altered in the presence of mutant huntingtin. It remains unclear whether mGluR5 can modulate Wnt and REST/NRSF signaling under physiological conditions and whether this modulation is altered in Huntington's disease (HD). Using primary corticostriatal neurons derived from wild type mouse embryos, we find that targeting mGluR5 using the agonist, DHPG, or the negative allosteric modulator, CTEP, modulates REST/NRSF expression by regulating the assembly of N-cadherin/ β-catenin complex in a Src kinase-dependent manner. We have validated our in vitro findings in vivo using two HD mouse models. Specifically, we show that pharmacological inhibition of mGluR5 in zQ175 mice and genetic ablation of mGluR5 in BACHD mice corrected the pathological activation of Src and rescued REST/NRSF-dependent signaling. Together, our data provide evidence that mGluR5 regulates REST/NRSF expression via the Wnt pathway and highlight the contribution of impaired REST/ NRSF signaling to HD pathology.
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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.