title: Metabotropic glutamate receptors and neurodegenerative diseases.
abstract: Glutamate is the most important excitatory neurotransmitter of the mammalian central nervous system (CNS), playing an important role in memory, synaptic plasticity and neuronal development. However, glutamate overstimulation is also implicated in neuronal cell death. There are two major types of glutamate receptors: ionotropic and metabotropic. Thus far, eight metabotropic glutamate receptors (mGluRs) subtypes have been characterized and are divided into three subgroups based on sequence homology and cell signaling activation. mGluRs activate a wide variety of cell signaling pathways by G protein-coupled pathways or via G protein-independent cell signaling activation. Moreover, these receptors exhibit widespread distribution in the CNS and are implicated in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease (HD). This review aims to discuss the latest updates concerning mGluRs and their role in neurodegenerative diseases. mGluRs agonists and antagonists as well as positive and negative allosteric modulators have been tested in several animal models of neurodegenerative diseases. Furthermore, mGluR knockout mouse models have been crossed to mouse models of AD and HD, providing important data about mGluRs role in neurodegenerative disease progression. Thus, mGluRs constitute potential therapeutic targets for the development of therapies to treat neurodegenerative diseases.
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil.
authors.forename: Fabiola M
authors.initials: FM
authors.lastname: Ribeiro
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil.
authors.forename: Luciene B
authors.initials: LB
authors.lastname: Vieira
authors.affiliation: Department of Physiological Sciences, Health Science Center, Universidade Federal do Espirito Santo, Vitoria, 29043-910, Brazil.
authors.forename: Rita G W
authors.initials: RG
authors.lastname: Pires
authors.affiliation: Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901, Brazil.
authors.forename: Roenick P
authors.initials: RP
authors.lastname: Olmo
authors.affiliation: University of Ottawa Brain and Mind Institute and Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, K1H 8M5, Canada. Electronic address: sferguso@uottawa.ca.
authors.forename: Stephen S G
authors.initials: SS
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018377:Neurotransmitter Agents; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid
keywords: Alzheimer’s disease; Glutamate; Huntington’s disease; Parkinson’s disease; mGluRs