Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease
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 microgl...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-024-00860-6 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Luisa Di Menna |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4bf739d04c2c47d4921b22e32fb63248 |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-4bf739d04c2c47d4921b22e32fb632482025-01-05T12:12:03ZengNature Portfolionpj Parkinson's Disease2373-80572025-01-0111111410.1038/s41531-024-00860-6Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s diseaseLuisa Di Menna0Marika Alborghetti1Maria Ilenia De Bartolo2Marina Borro3Giovanna Gentile4Manuela Zinni5Matteo Bologna6Carolina Cutrona7Giovanna D’Errico8Tiziana Imbriglio9Domenico Bucci10Sara Merlo11Roxana Paula Ginerete12Rosamaria Orlando13Federica Carrillo14Giorgio Fortunato15Milena Cannella16Maria Angela Sortino17Julien Pansiot18Olivier Baud19Ferdinando Nicoletti20Valeria Bruno21Maurizio Simmaco22Francesco Ernesto Pontieri23Edoardo Bianchini24Domiziana Rinaldi25Amalia de Curtis26Giovanni De Gaetano27Licia Iacoviello28Teresa Esposito29Alfredo Berardelli30Giuseppe Battaglia31Department of Molecular Pathology, IRCCS NeuromedDepartments of Human Neurosciences, Sapienza University of RomeDepartment of Clinical Neurophysiology, IRCCS NeuromedNeuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of RomeNeuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of RomeInserm UMR1141 NeuroDiderot, Université Paris CitéDepartments of Human Neurosciences, Sapienza University of RomeDepartments of Human Neurosciences, Sapienza University of RomeDepartment of Molecular Pathology, IRCCS NeuromedDepartment of Molecular Pathology, IRCCS NeuromedDepartment of Molecular Pathology, IRCCS NeuromedDepartment of Drug and Health Sciences, University of CataniaDepartment of Molecular Pathology, IRCCS NeuromedDepartment of Molecular Pathology, IRCCS NeuromedInstitute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research CouncilInstitute of Genetics and Biophysics, Adriano Buzzati-Traverso, National Research CouncilDepartment of Molecular Pathology, IRCCS NeuromedDepartment of Biomedical and Biotechnological Sciences, University of CataniaInserm UMR1141 NeuroDiderot, Université Paris CitéInserm UMR1141 NeuroDiderot, Université Paris CitéDepartment of Molecular Pathology, IRCCS NeuromedDepartment of Molecular Pathology, IRCCS NeuromedNeuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of RomeNeuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of RomeNeuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of RomeNeuroscience, Mental Health, and Sensory Organs Clinical Neurophysiology, Sapienza University of RomeDepartment of Epidemiology and Prevention, IRCCS NeuromedDepartment of Epidemiology and Prevention, IRCCS NeuromedDepartment of Epidemiology and Prevention, IRCCS NeuromedDepartment of Molecular Pathology, IRCCS NeuromedDepartments of Human Neurosciences, Sapienza University of RomeDepartment of Molecular Pathology, IRCCS NeuromedAbstract 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.https://doi.org/10.1038/s41531-024-00860-6 |
| spellingShingle | 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 Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease npj Parkinson's Disease |
| title | Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease |
| title_full | Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease |
| title_fullStr | Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease |
| title_full_unstemmed | Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease |
| title_short | Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson’s disease |
| title_sort | preclinical and clinical study on type 3 metabotropic glutamate receptors in parkinson s disease |
| url | https://doi.org/10.1038/s41531-024-00860-6 |
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