Dynamics and modulation of metabotropic glutamate receptors. 2015

Philippe Rondard, and Jean-Philippe Pin
CNRS, UMR5203, Institut de Génomique Fonctionnelle, Montpellier, France; INSERM, U661, Montpellier, France; Université Montpellier 1 & 2, Montpellier F-34000, France. Electronic address: philippe.rondard@igf.cnrs.fr.

The metabotropic glutamate receptors (mGluRs) are glutamate-activated G protein-coupled receptors widely expressed in the central nervous system. The eight mGluRs subtypes modulate transmission at many synapses, and are interesting therapeutic targets for the treatment of many neurological and psychiatric diseases. In particular, their organization in multiple domains and subunits offers various possibilities for the development of drugs that modulate mGluRs activity with different efficacies. Recent structural, biophysical and functional analyses have provided new insights into the mechanism of mGluR activation and dynamics. They also revealed the structural bases of ligand efficacy then providing possible mechanism of action of partial agonists and allosteric modulators. These new findings are of great interest for the development of novel mGluR subtype-selective compounds.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D009422 Nervous System Diseases Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle. Neurologic Disorders,Nervous System Disorders,Neurological Disorders,Disease, Nervous System,Diseases, Nervous System,Disorder, Nervous System,Disorder, Neurologic,Disorder, Neurological,Disorders, Nervous System,Disorders, Neurologic,Disorders, Neurological,Nervous System Disease,Nervous System Disorder,Neurologic Disorder,Neurological Disorder
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D002490 Central Nervous System The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000494 Allosteric Regulation The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES. Regulation, Allosteric,Allosteric Regulations,Regulations, Allosteric
D001523 Mental Disorders Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. Mental Illness,Psychiatric Diseases,Psychiatric Disorders,Psychiatric Illness,Behavior Disorders,Diagnosis, Psychiatric,Mental Disorders, Severe,Psychiatric Diagnosis,Illness, Mental,Mental Disorder,Mental Disorder, Severe,Mental Illnesses,Psychiatric Disease,Psychiatric Disorder,Psychiatric Illnesses,Severe Mental Disorder,Severe Mental Disorders
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D058990 Molecular Targeted Therapy Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease. Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular
D018094 Receptors, Metabotropic Glutamate Cell surface proteins that bind glutamate and act through G-proteins to influence second messenger systems. Several types of metabotropic glutamate receptors have been cloned. They differ in pharmacology, distribution, and mechanisms of action. Glutamate Receptors, Metabotropic,Metabotropic Glutamate Receptors,Receptors, Glutamate, Metabotropic,Metabotropic Glutamate Receptor,Glutamate Receptor, Metabotropic,Receptor, Metabotropic Glutamate

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