Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Expression of genes encoding anti-inflammatory proteins and neuroprotective factors was reduced in the striatum of MPTP-treated mGlu3 mice. We also examined polymorphic variants of GRM3 (the mGlu3 receptor encoding gene) in 723 PD patients and 826 healthy controls. Two GRM3 haplotypes were associated with PD, and gene variants correlated with motor and non-motor signs. Interestingly, PD patients carrying each of the two haplotypes showed an impaired cortical plasticity in the paired associated stimulation paradigm of magnetic transcranial stimulation. These findings suggest that mGlu3 receptors are neuroprotective in mouse models of parkinsonism and shape mechanisms of cortical plasticity in PD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/s41531-024-00860-6 | DOI Listing |
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700162 | PMC |
Publication Analysis
Top Keywords
Similar Publications
Esketamine-mediated alleviation of electroconvulsive shock-induced memory impairment is associated with the regulation of mGluR5 in depressive-like rats.
Pharmacol Biochem Behav
January 2025
Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address:
Electroconvulsive therapy (ECT) is recognized as one of the most efficacious interventions for depression. However, it is associated with impairments in learning and memory functions. Ketamine has demonstrated potential in mitigating cognitive deficits.
View Article and Find Full Text PDFPreclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.
NPJ Parkinsons Dis
January 2025
Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy.
Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
View Article and Find Full Text PDFNon-canonical signaling initiated by hormone-responsive G protein-coupled receptors from subcellular compartments.
Pharmacol Ther
December 2024
Fang Zongxi Center for Marine EvoDevo, MoE Key Laboratory of Marine Genetics and Breeding, College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China; Insititute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.. Electronic address:
G protein-coupled receptors (GPCRs), the largest family of membrane receptors in the mammalian genomes, regulate almost all known physiological processes by transducing numerous extracellular stimuli including almost two-thirds of endogenous hormones and neurotransmitters. The traditional view held that GPCR signaling occurs exclusively at the cell surface, where the receptors bind with the ligands and undergo conformational changes to recruit and activate heterotrimeric G proteins. However, with the application of advanced biochemical and biophysical techniques, this conventional model is challenged by the elucidation of spatiotemporal GPCR activation with the evidence that receptors can signal from subcellular compartments to exhibit various molecular and cellular responses with physiological and pathophysiological relevance.
View Article and Find Full Text PDFA-mediated synaptic glutamate dynamics and calcium dynamics in astrocytes associated with Alzheimer's disease.
Cogn Neurodyn
December 2024
School of Mathematics and Statistics, Shaanxi Normal University, Xi'an, 710119 People's Republic of China.
The accumulation of amyloid peptide is assumed to be one of the main causes of Alzheimer's disease . There is increasing evidence that astrocytes are the primary targets of A. A can cause abnormal synaptic glutamate, aberrant extrasynaptic glutamate, and astrocytic calcium dysregulation through astrocyte glutamate transporters facing the synaptic cleft (GLT-syn), astrocyte glutamate transporters facing the extrasynaptic space (GLT-ess), metabotropic glutamate receptors in astrocytes (mGluR), N-methyl-D-aspartate receptors in astrocytes (NMDAR), and glutamatergic gliotransmitter release (Glio-Rel).
View Article and Find Full Text PDFPharmacology, Signaling and Therapeutic Potential of Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators.
ACS Pharmacol Transl Sci
December 2024
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Parkville, VIC 3052, Australia.
Metabotropic glutamate receptors are a family of eight class C G protein-coupled receptors regulating higher order brain functions including cognition and motion. Metabotropic glutamate receptors have thus been heavily investigated as potential drug targets for treating neurological disorders. Drug discovery efforts directed toward metabotropic glutamate receptor subtype 5 (mGlu) have been particularly fruitful, with a wealth of drug candidates and pharmacological tools identified.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!