Glutamate is a fundamental excitatory neurotransmitter in the mammalian centralnervous system (CNS), playing key roles in memory, neuronal development, and synapticplasticity. Moreover, excessive glutamate release has been implicated in neuronal celldeath. There are both ionotropic and metabotropic glutamate receptors (mGluRs), thelatter of which can be divided into eight subtypes and three subgroups based onhomology sequence and their effects on cell signaling. Indeed, mGluRs exert fine controlover glutamate activity by stimulating several cell-signaling pathwaysviathe activationof G protein-coupled (GPC) or G protein-independent cell signaling. The involvementof specific mGluRs in different forms of synaptic plasticity suggests that modulationof mGluRs may aid in the treatment of cognitive impairments related to severalneurodevelopmental/psychiatric disorders and neurodegenerative diseases, which areassociated with a high economic and social burden. Preclinical and clinical data haveshown that, in the CNS, mGluRs are able to modulate presynaptic neurotransmissionby fine-tuning neuronal firing and neurotransmitter release in a dynamic, activity-dependent manner. Current studies on drugs that target mGluRs have identifiedpromising, innovative pharmacological tools for the treatment of neurodegenerative andneuropsychiatric conditions, including chronic pain.

Role of metabotropic glutamate receptors in neurological disorders

Crupi R.
Co-primo
;
Impellizzeri D.
Co-primo
;
Cuzzocrea S.
Ultimo
2019-01-01

Abstract

Glutamate is a fundamental excitatory neurotransmitter in the mammalian centralnervous system (CNS), playing key roles in memory, neuronal development, and synapticplasticity. Moreover, excessive glutamate release has been implicated in neuronal celldeath. There are both ionotropic and metabotropic glutamate receptors (mGluRs), thelatter of which can be divided into eight subtypes and three subgroups based onhomology sequence and their effects on cell signaling. Indeed, mGluRs exert fine controlover glutamate activity by stimulating several cell-signaling pathwaysviathe activationof G protein-coupled (GPC) or G protein-independent cell signaling. The involvementof specific mGluRs in different forms of synaptic plasticity suggests that modulationof mGluRs may aid in the treatment of cognitive impairments related to severalneurodevelopmental/psychiatric disorders and neurodegenerative diseases, which areassociated with a high economic and social burden. Preclinical and clinical data haveshown that, in the CNS, mGluRs are able to modulate presynaptic neurotransmissionby fine-tuning neuronal firing and neurotransmitter release in a dynamic, activity-dependent manner. Current studies on drugs that target mGluRs have identifiedpromising, innovative pharmacological tools for the treatment of neurodegenerative andneuropsychiatric conditions, including chronic pain.
2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3150176
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