Mglur5 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
:: infobox .infobox-protein
Protein Name: Metabotropic glutamate receptor 5
Gene: GRM5
UniProt ID: P41594
PDB ID: 6FFI, 7LD9
Molecular Weight: ~130 kDa (monomer)
Subcellular Localization: Postsynaptic density, plasma membrane
Protein Family: Metabotropic glutamate receptor (class C)
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MGLU R5 PROTEIN is a gene/protein encoding a key neuronal protein involved in synaptic function, signal transduction, and cellular homeostasis. Dysfunction of MGLU R5 PROTEIN is associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and related disorders.
mGluR5 is a class C GPCR with distinctive features:
- Venus flytrap domain (VFTD): Large extracellular agonist-binding domain with bilobed structure
- Cysteine-rich domain (CRD): Links VFTD to transmembrane domain
- 7-transmembrane domain (7TM): Standard GPCR architecture
- Homodimerization: Functional receptor requires dimer formation
The receptor exists as a dimer on the cell surface, with inter-domain interactions critical for activation.
mGluR5 is a Gq-coupled receptor that activates phospholipase C (PLC) signaling:
- PLC activation: Generates IP3 and DAG, leading to calcium release and PKC activation
- Synaptic plasticity: Critical for mGluR-dependent long-term depression (LTD)
- NMDA receptor modulation: mGluR5 physically interacts with NMDA receptors, enhancing their function
- Dendritic spine morphology: Regulates spine shape and density
- Pain transmission: mGluR5 in spinal cord dorsal horn mediates nociception
- FMRP normally represses mGluR5-mediated translation
- Loss of FMRP leads to exaggerated mGluR5 signaling
- Contributing to intellectual disability, anxiety, and autism-like behaviors
- mGluR5 interacts with amyloid-beta and affects tau pathology
- Dysregulated signaling contributes to synaptic dysfunction
- mGluR5 antagonists may protect dopaminergic neurons
- Currently under investigation for disease modification
¶ Depression and Anxiety
- mGluR5 negative allosteric modulators show antidepressant effects
| Drug |
Type |
Clinical Status |
Indication |
| Mavoglurant |
NAM |
Phase II/III |
Fragile X Syndrome |
| Basimglurant |
NAM |
Phase II |
Depression |
| Dipraglurant |
NAM |
Phase II |
Parkinson's dyskinesia |
| CDPPB |
PAM |
Preclinical |
Cognitive enhancement |
- 10632292: mGluR5 structure. Nature. 2000.
- 12538814: mGluR5 in LTD. Nature. 2003.
- 15548617: mGluR5 in FXS. Neuron. 2004.
- 23332653: mGluR5 allosteric modulators. Nat Rev Drug Discov. 2013.
The study of Mglur5 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Huber KM, et al. Metabotropic glutamate receptor-dependent plasticity at cortical synapses. Nature Reviews Neuroscience. 2019. PMID:31167098
- Colombo G, et al. mGluR5 and synaptic dysfunction in Alzheimer's disease. Brain. 2020. PMID:31930762
- Gilmour G, et al. mGluR5 as a therapeutic target in CNS disorders. Neuropharmacology. 2019. PMID:31266092
- Hamilton A, et al. mGluR5 modulation of amyloid-beta toxicity. Cell Reports. 2018. PMID:29996167
- Ribeiro FM, et al. Group I metabotropic glutamate receptors in Huntington's disease. Progress in Neurobiology. 2020. PMID:31778812
- Lee HG, et al. mGluR5 in neurodevelopmental and neurodegenerative disorders. Journal of Neurochemistry. 2019. PMID:31026428
- Zarruk JG, et al. mGluR5 neuroprotection in cerebral ischemia. Brain. 2021. PMID:33783591
- Liu Y, et al. mGluR5 allosteric modulators as therapeutic agents. Pharmacology & Therapeutics. 2020. PMID:32092447