npj Parkinson's Disease (Jan 2025)
Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease
- Luisa Di Menna,
- Marika Alborghetti,
- Maria Ilenia De Bartolo,
- Marina Borro,
- Giovanna Gentile,
- Manuela Zinni,
- Matteo Bologna,
- Carolina Cutrona,
- Giovanna D’Errico,
- Tiziana Imbriglio,
- Domenico Bucci,
- Sara Merlo,
- Roxana Paula Ginerete,
- Rosamaria Orlando,
- Federica Carrillo,
- Giorgio Fortunato,
- Milena Cannella,
- Maria Angela Sortino,
- Julien Pansiot,
- Olivier Baud,
- Ferdinando Nicoletti,
- Valeria Bruno,
- Maurizio Simmaco,
- Francesco Ernesto Pontieri,
- Edoardo Bianchini,
- Domiziana Rinaldi,
- Amalia de Curtis,
- Giovanni De Gaetano,
- Licia Iacoviello,
- Teresa Esposito,
- Alfredo Berardelli,
- Giuseppe Battaglia
Affiliations
- Luisa Di Menna
- Department of Molecular Pathology, IRCCS Neuromed
- Marika Alborghetti
- Departments of Human Neurosciences, Sapienza University of Rome
- Maria Ilenia De Bartolo
- Department of Clinical Neurophysiology, IRCCS Neuromed
- Marina Borro
- Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome
- Giovanna Gentile
- Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome
- Manuela Zinni
- Inserm UMR1141 NeuroDiderot, Université Paris Cité
- Matteo Bologna
- Departments of Human Neurosciences, Sapienza University of Rome
- Carolina Cutrona
- Departments of Human Neurosciences, Sapienza University of Rome
- Giovanna D’Errico
- Department of Molecular Pathology, IRCCS Neuromed
- Tiziana Imbriglio
- Department of Molecular Pathology, IRCCS Neuromed
- Domenico Bucci
- Department of Molecular Pathology, IRCCS Neuromed
- Sara Merlo
- Department of Drug and Health Sciences, University of Catania
- Roxana Paula Ginerete
- Department of Molecular Pathology, IRCCS Neuromed
- Rosamaria Orlando
- Department of Molecular Pathology, IRCCS Neuromed
- Federica Carrillo
- Institute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research Council
- Giorgio Fortunato
- Institute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research Council
- Milena Cannella
- Department of Molecular Pathology, IRCCS Neuromed
- Maria Angela Sortino
- Department of Biomedical and Biotechnological Sciences, University of Catania
- Julien Pansiot
- Inserm UMR1141 NeuroDiderot, Université Paris Cité
- Olivier Baud
- Inserm UMR1141 NeuroDiderot, Université Paris Cité
- Ferdinando Nicoletti
- Department of Molecular Pathology, IRCCS Neuromed
- Valeria Bruno
- Department of Molecular Pathology, IRCCS Neuromed
- Maurizio Simmaco
- Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome
- Francesco Ernesto Pontieri
- Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome
- Edoardo Bianchini
- Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome
- Domiziana Rinaldi
- Neuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of Rome
- Amalia de Curtis
- Department of Epidemiology and Prevention, IRCCS Neuromed
- Giovanni De Gaetano
- Department of Epidemiology and Prevention, IRCCS Neuromed
- Licia Iacoviello
- Department of Epidemiology and Prevention, IRCCS Neuromed
- Teresa Esposito
- Department of Molecular Pathology, IRCCS Neuromed
- Alfredo Berardelli
- Departments of Human Neurosciences, Sapienza University of Rome
- Giuseppe Battaglia
- Department of Molecular Pathology, IRCCS Neuromed
- DOI
- https://doi.org/10.1038/s41531-024-00860-6
- Journal volume & issue
-
Vol. 11,
no. 1
pp. 1 – 14
Abstract
Abstract 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.
