ArticleThe Journal of experimental medicine2021
Neuronal metabotropic glutamate receptor 8 protects against neurodegeneration in CNS inflammation.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 47 citations in OpenAlex.
- Structural basis of active state coupling of metabotropic glutamate receptor 8 to beta-arrestins.Nature communications · 2026Article
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- Mitochondrial-endoplasmic reticulum interactions in lung diseases.Cell death & disease · 2026Review
- The presynaptic protein bassoon is a biofluid biomarker of synaptic pathology in multiple sclerosis.EBioMedicine · 2026Article
- 1,3,4 oxadiazole derivative attenuates neurotransmitter-mediated inflammatory response in EAE model of multiple sclerosis.Scientific reports · 2026Article
- Serum Amino Acid and Fatty Acid Metabolites as Predictors of Sleep Disorders in Children: A Risk Prediction Model.Biomedicines · 2026Article
- Neuronal antibody targeting metabotropic glutamate receptor 8 in five cases and its pathogenicity.Journal of neurology · 2026Article
- Brain capillary endothelial-like cells show altered barrier functionality and reduced transport of amyloid β in late-onset Alzheimer disease.Fluids and barriers of the CNS · 2026Article
- Modulating glutamate neurotransmission inFrontiers in immunology · 2026Review
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- Intercellular signaling and synaptic deconstruction uncovered by single-cell and spatial transcriptomics in an AD tauopathy model.Communications biology · 2025Article
- Development of a Human Preclinical Platform for the Identification of Neuroprotective Compounds.The European journal of neuroscience · 2025Article
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- Escape from TGF-β-induced senescence promotes aggressive hallmarks in epithelial hepatocellular carcinoma cells.Molecular oncology · 2025Article
- Human CLOCK enhances neocortical function.Nature neuroscience · 2025Article
- Comparative Analysis of Human Brain RNA-seq Reveals the Combined Effects of Ferroptosis and Autophagy on Alzheimer's Disease in Multiple Brain Regions.Molecular neurobiology · 2025Article
- Screening and Verification COPD-OSA Overlap Syndrome Core Genes Using Bioinformatics.International journal of chronic obstructive pulmonary disease · 2025Article
- Genetic evidence informs the direction of therapeutic modulation in drug development.npj drug discovery · 2025Article
- Identification and development of TRPM4 antagonists to counteract neuronal excitotoxicity.iScience · 2024Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with continuous neuronal loss. Treatment of clinical progression remains challenging due to lack of insights into inflammation-induced neurodegenerative pathways. Here, we show that an imbalance in the neuronal receptor interactome is driving glutamate excitotoxicity in neurons of MS patients and identify the MS risk-associated metabotropic glutamate receptor 8 (GRM8) as a decisive modulator. Mechanistically, GRM8 activation counteracted neuronal cAMP accumulation, thereby directly desensitizing the inositol 1,4,5-trisphosphate receptor (IP3R). This profoundly limited glutamate-induced calcium release from the endoplasmic reticulum and subsequent cell death. Notably, we found Grm8-deficient neurons to be more prone to glutamate excitotoxicity, whereas pharmacological activation of GRM8 augmented neuroprotection in mouse and human neurons as well as in a preclinical mouse model of MS. Thus, we demonstrate that GRM8 conveys neuronal resilience to CNS inflammation and is a promising neuroprotective target with broad therapeutic implications.
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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.