title: Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism.
abstract: Activation of group-I metabotropic glutamate receptors, mGlu1 and mGlu5, triggers a variety of signalling pathways in neurons and glial cells, which are differently implicated in synaptic plasticity. The earliest and much of key studies discovered abnormal mGlu5 receptor function in Fragile X syndrome (FXS) mouse models which then motivated more recent work that finds mGlu5 receptor dysfunction in related disorders such as intellectual disability (ID), obsessive-compulsive disorder (OCD) and autism. Therefore, mGlu1/5 receptor dysfunction may represent a common aetiology of these complex diseases. Furthermore, many studies have focused on dysregulation of mGlu5 signalling to synaptic protein synthesis. However, emerging evidence finds abnormal mGlu5 receptor interactions with its scaffolding proteins in FXS which results in mGlu5 receptor dysfunction and phenotypes independent of signalling to protein synthesis. Finally, both an increased and reduced mGlu5 functioning seem to be associated with ID and autism spectrum disorders, with important consequences for potential treatment of these developmental disorders.
authors.affiliation: Institute of Neurological Sciences, the National Research Council of Italy (CNR), Catania, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: D'Antoni
authors.affiliation: Institute of Neurological Sciences, the National Research Council of Italy (CNR), Catania, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Spatuzza
authors.affiliation: IRCCS Oasi Maria SS, Troina (EN), Italy.
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Bonaccorso
authors.affiliation: IRCCS Oasi Maria SS, Troina (EN), Italy.
authors.forename: Sebastiano A
authors.initials: SA
authors.lastname: Musumeci
authors.affiliation: Department of Biomedical Sciences, section of Physiology, University of Catania, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciranna
authors.affiliation: IRCCS Neuromed, Pozzilli (IS), Italy; University of Rome La Sapienza, Rome, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
authors.affiliation: University of Texas Southwestern Medical Center, Department of Neuroscience, Dallas, TX 75390-9111, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Huber
authors.affiliation: Institute of Neurological Sciences, the National Research Council of Italy (CNR), Catania, Italy; IRCCS Oasi Maria SS, Troina (EN), Italy. Electronic address: mariavincenza.catania@cnr.it.
authors.forename: Maria Vincenza
authors.initials: MV
authors.lastname: Catania
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000378:metabolism*; D006801:Humans; D008607:Intellectual Disability / Q000378:metabolism*; D009473:Neuronal Plasticity; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1
keywords: Developmental disorders; Fmrp; Fragile X; Homer; Mental retardation; Neuroligin; PTEN; SAPAP3; SHANK; Synaptic plasticity; TSC