title: Positive allosteric modulators of metabotropic glutamate 2 receptors in schizophrenia treatment.
abstract: The past two decades have witnessed a rise in the 'NMDA receptor hypofunction' hypothesis for schizophrenia, a devastating disorder that affects around 1% of the population worldwide. A variety of presynaptic, postsynaptic, and regulatory proteins involved in glutamatergic signaling have thus been proposed as potential therapeutic targets. This review focuses on positive allosteric modulation of metabotropic glutamate 2 receptors (mGlu2Rs) and discusses how recent preclinical epigenetic data may provide a molecular explanation for the discrepant results of clinical studies, further stimulating the field to exploit the promise of mGlu2R as a target for schizophrenia treatment.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Amr
authors.initials: A
authors.lastname: Ellaithy
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Younkin
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; Departments of Psychiatry and Neurology, and The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: jgmaeso@vcu.edu.
authors.forename: Javier
authors.initials: J
authors.lastname: González-Maeso
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address: delogothetis@vcu.edu.
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects*; D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D020239:Receptor Cross-Talk; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D018690:Excitatory Amino Acid Agonists; D044402:Receptor, Serotonin, 5-HT2A; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2
keywords: 5-HT(2A); HDAC2; PAMs; epigenetics; mGlu(2)R; schizophrenia