Dysregulation of group-I metabotropic glutamate (mGlu) receptor mediated signalling in disorders associated with Intellectual Disability and Autism

Simona D'Antoni, Michela Spatuzza, Carmela M. Bonaccorso, Sebastiano A. Musumeci, Lucia Ciranna, Ferdinando Nicoletti, Kimberly M. Huber, Maria Vincenza Catania

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)228-241
Number of pages14
JournalNeuroscience and Biobehavioral Reviews
Volume46
Issue numberP2
DOIs
Publication statusPublished - Oct 1 2014

Keywords

  • Developmental disorders
  • Fmrp
  • Fragile X
  • Homer
  • Mental retardation
  • Neuroligin
  • PTEN
  • SAPAP3
  • SHANK
  • Synaptic plasticity
  • TSC

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Cognitive Neuroscience
  • Neuropsychology and Physiological Psychology
  • Medicine(all)

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