Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Autor: Di Menna L; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Alborghetti M; Departments of Human Neurosciences, Sapienza University of Rome, Rome, Italy.; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy., De Bartolo MI; Department of Clinical Neurophysiology, IRCCS Neuromed, Pozzilli, Italy., Borro M; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy., Gentile G; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy., Zinni M; Inserm UMR1141 NeuroDiderot, Université Paris Cité, Paris, France., Bologna M; Departments of Human Neurosciences, Sapienza University of Rome, Rome, Italy.; Department of Clinical Neurophysiology, IRCCS Neuromed, Pozzilli, Italy., Cutrona C; Departments of Human Neurosciences, Sapienza University of Rome, Rome, Italy., D'Errico G; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Imbriglio T; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Bucci D; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Merlo S; Department of Drug and Health Sciences, University of Catania, Catania, Italy., Ginerete RP; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Orlando R; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Carrillo F; Institute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research Council, Naples, Italy., Fortunato G; Institute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research Council, Naples, Italy., Cannella M; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy., Sortino MA; Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy., Pansiot J; Inserm UMR1141 NeuroDiderot, Université Paris Cité, Paris, France., Baud O; Inserm UMR1141 NeuroDiderot, Université Paris Cité, Paris, France.; Department of Neonatal Medicine, Cochin-Port Royal Hospital, FHU PREMA, AP-HP Centre, Paris, France.; Université Paris Cite, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPE, French Institute for Medical Research and Health INSERM, INRAE, 75014, Paris, France., Nicoletti F; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy.; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy., Bruno V; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy.; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy., Simmaco M; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy., Pontieri FE; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy., Bianchini E; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy.; AGEIS, Université Grenoble Alpes, 38000, Grenoble, France., Rinaldi D; Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome, Rome, Italy., de Curtis A; Department of Epidemiology and Prevention, IRCCS Neuromed, 86077, Pozzilli, Italy., De Gaetano G; Department of Epidemiology and Prevention, IRCCS Neuromed, 86077, Pozzilli, Italy., Iacoviello L; Department of Epidemiology and Prevention, IRCCS Neuromed, 86077, Pozzilli, Italy.; Department of Medicine and Surgery, LUM University, 70010, Casamassima, Bari, Italy., Esposito T; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy.; Institute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research Council, Naples, Italy., Berardelli A; Departments of Human Neurosciences, Sapienza University of Rome, Rome, Italy. alfredo.berardelli@uniroma1.it.; Department of Clinical Neurophysiology, IRCCS Neuromed, Pozzilli, Italy. alfredo.berardelli@uniroma1.it., Battaglia G; Department of Molecular Pathology, IRCCS Neuromed, Pozzilli, Italy.; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Jazyk: angličtina
Zdroj: NPJ Parkinson's disease [NPJ Parkinsons Dis] 2025 Jan 04; Vol. 11 (1), pp. 9. Date of Electronic Publication: 2025 Jan 04.
DOI: 10.1038/s41531-024-00860-6
Abstrakt: 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.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2025. The Author(s).)
Databáze: MEDLINE
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