title: The impact of metabotropic glutamate receptors into active neurodegenerative processes: A "dark side" in the development of new symptomatic treatments for neurologic and psychiatric disorders.
abstract: Metabotropic glutamate (mGlu) receptor ligands are under clinical development for the treatment of CNS disorders with high social and economic burden, such as schizophrenia, major depressive disorder (MDD), and Parkinson's disease (PD), and are promising drug candidates for the treatment of Alzheimer's disease (AD). So far, clinical studies have shown symptomatic effects of mGlu receptor ligands, but it is unknown whether these drugs act as disease modifiers or, at the opposite end, they accelerate disease progression by enhancing neurodegeneration. This is a fundamental issue in the treatment of PD and AD, and is also an emerging theme in the treatment of schizophrenia and MDD, in which neurodegeneration is also present and contribute to disease progression. Moving from in vitro data and preclinical studies, we discuss the potential impact of drugs targeting mGlu2, mGlu3, mGlu4 and mGlu5 receptor ligands on active neurodegeneration associated with AD, PD, schizophrenia, and MDD. We wish to highlight that our final comments on the best drug candidates are not influenced by commercial interests or by previous or ongoing collaborations with drug companies. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.
authors.affiliation: Department of Physiology and Pharmacology, University Sapienza, 00185 Rome, Italy; I.R.C.C.S. Neuromed, 86077 Pozzilli, Italy. Electronic address: valeria.bruno@uniroma1.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
authors.affiliation: Department of Drug Sciences, University of Catania, 95125 Catania, Italy; I.R.C.C.S. Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging, 94018 Troina, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.affiliation: Department of Drug Sciences, University of Catania, 95125 Catania, Italy; National Research Council, Institute of Biostructure and Bioimaging (IBB-CNR), 95126 Catania, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Copani
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, USA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Matrisciano
authors.affiliation: Department of Physiology and Pharmacology, University Sapienza, 00185 Rome, Italy; I.R.C.C.S. Neuromed, 86077 Pozzilli, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: I.R.C.C.S. Neuromed, 86077 Pozzilli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D016503:Drug Delivery Systems / Q000639:trends; D055808:Drug Discovery / Q000639:trends*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism*; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate
keywords: Alzhiemer’s disease; Major depressive disorders; Metabotropic glutamate receptors; Neurodegeneration; Parkinson’s disease; Schizophrenia