: 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.
Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease / Di Menna, Luisa; Alborghetti, Marika; De Bartolo, Maria Ilenia; Borro, Marina; Gentile, Giovanna; Zinni, Manuela; Bologna, Matteo; Cutrona, Carolina; D'Errico, Giovanna; Imbriglio, Tiziana; Bucci, Domenico; Merlo, Sara; Ginerete, Roxana Paula; Orlando, Rosamaria; Carrillo, Federica; Fortunato, Giorgio; Cannella, Milena; Sortino, Maria Angela; Pansiot, Julien; Baud, Olivier; Nicoletti, Ferdinando; Bruno, Valeria; Simmaco, Maurizio; Pontieri, Francesco Ernesto; Bianchini, Edoardo; Rinaldi, Domiziana; de Curtis, Amalia; De Gaetano, Giovanni; Iacoviello, Licia; Esposito, Teresa; Berardelli, Alfredo; Battaglia, Giuseppe. - In: NPJ PARKINSON'S DISEASE. - ISSN 2373-8057. - 11:1(2025), p. 1. [10.1038/s41531-024-00860-6]
Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease
Alborghetti, Marika;De Bartolo, Maria Ilenia;Borro, Marina;Gentile, Giovanna;Bologna, Matteo;Cutrona, Carolina;Ginerete, Roxana Paula;Orlando, Rosamaria;Nicoletti, Ferdinando;Bruno, Valeria;Simmaco, Maurizio;Pontieri, Francesco Ernesto;Bianchini, Edoardo;Rinaldi, Domiziana;Berardelli, Alfredo
;Battaglia, Giuseppe
2025
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
