ArticleBrain : a journal of neurology2016
Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signalling in Alzheimer's disease.
Article in Brain : a journal of neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 138 citations in OpenAlex.
- Distinct Filament Conformation for Receptor-Bound Amyloid-β from Alzheimer's Disease Brain.Nature communications · 2026Article
- Synaptic activity controls local exposure of an 'eat-me' signal via ANO3-ITPR1 signaling.bioRxiv : the preprint server for biology · 2026Article
- PrPStem cell reports · 2026Article
- Presymptomatic pharmacological inhibition of mGluR5 improves survival in a mouse model of prion diseases.Acta neuropathologica communications · 2026Article
- Distinct Filament Conformation for Receptor-Bound Amyloid-ß from Alzheimer's Disease Brain.bioRxiv : the preprint server for biology · 2025Article
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Single-Cell Transcriptomic Profiling Reveals Regional Differences in the Prefrontal and Entorhinal Cortex of Alzheimer's Disease Brain.International journal of molecular sciences · 2025Article
- Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice.The Journal of clinical investigation · 2025Article
- Assessment of the relationship between synaptic density and metabotropic glutamate receptors in early Alzheimer's disease: a multi-tracer PET study.Alzheimer's research & therapy · 2025Article
- AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.Translational neurodegeneration · 2025Review
- Pharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.ACS pharmacology & translational science · 2024Review
- Cellular Prion Protein Conformational Shift after Liquid-Liquid Phase Separation Regulated by a Polymeric Antagonist and Mutations.Journal of the American Chemical Society · 2024Article
- New Light on Prions: Putative Role of PrPInternational journal of molecular sciences · 2024Review
- Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [Alzheimer's research & therapy · 2024Article
- Unraveling the intercellular communication disruption and key pathways in Alzheimer's disease: an integrative study of single-nucleus transcriptomes and genetic association.Alzheimer's research & therapy · 2024Article
- Article
- Neuronal transcriptome, tau and synapse loss in Alzheimer's knock-in mice require prion protein.Alzheimer's research & therapy · 2023Article
- Unraveling the intercellular communication disruption and key pathways in Alzheimer's disease: An integrative study of single-nucleus transcriptomes and genetic association.Research square · 2023Article
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- Detecting Early Cognitive Decline in Alzheimer's Disease with Brain Synaptic Structural and Functional Evaluation.Biomedicines · 2023Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Alzheimer's disease-related phenotypes in mice can be rescued by blockade of either cellular prion protein or metabotropic glutamate receptor 5. We sought genetic and biochemical evidence that these proteins function cooperatively as an obligate complex in the brain. We show that cellular prion protein associates via transmembrane metabotropic glutamate receptor 5 with the intracellular protein mediators Homer1b/c, calcium/calmodulin-dependent protein kinase II, and the Alzheimer's disease risk gene product protein tyrosine kinase 2 beta. Coupling of cellular prion protein to these intracellular proteins is modified by soluble amyloid-β oligomers, by mouse brain Alzheimer's disease transgenes or by human Alzheimer's disease pathology. Amyloid-β oligomer-triggered phosphorylation of intracellular protein mediators and impairment of synaptic plasticity in vitro requires Prnp-Grm5 genetic interaction, being absent in transheterozygous loss-of-function, but present in either single heterozygote. Importantly, genetic coupling between Prnp and Grm5 is also responsible for signalling, for survival and for synapse loss in Alzheimer's disease transgenic model mice. Thus, the interaction between metabotropic glutamate receptor 5 and cellular prion protein has a central role in Alzheimer's disease pathogenesis, and the complex is a potential target for disease-modifying intervention.
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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.