Group-I metabotropic glutamate receptors: Hypotheses to explain their dual role in neurotoxicity and neuroprotection

F. Nicoletti, V. Bruno, M. V. Catania, G. Battaglia, A. Copani, G. Barbagallo, V. Ceña, J. Sanchez-Prieto, P. F. Spano, M. Pizzi

Research output: Contribution to journalArticlepeer-review

Abstract

The role of group-I metabotropic glutamate receptors (mGlu1 and 5) in neurodegeneration is still controversial. While antagonists of these receptors are consistently neuroprotective, agonists have been found to either amplify or attenuate excitotoxic neuronal death. At least three variables affect responses to agonists: (i) the presence of the NR2C subunit in the NMDA receptor complex; (ii) the existence of an activity-dependent functional switch of group-I mGlu receptors, similar to that described for the regulation of glutamate release; and (iii) the presence of astrocytes expressing mGlu5 receptors. Thus, a number of factors, including the heteromeric composition of NMDA receptors, the exposure time to drugs or to ambient glutamate, and the function of astrocytes clearing extracellular glutamate and producing neurotoxic or neuroprotective factors, must be taken into account when examining the role of group-I mGlu receptors in neurodegeneration/neuroprotection.

Original languageEnglish
Pages (from-to)1477-1484
Number of pages8
JournalNeuropharmacology
Volume38
Issue number10
DOIs
Publication statusPublished - Oct 1999

Keywords

  • 'Functional switch'
  • Astrocytes
  • Group-I mGlu receptors
  • Neurodegeneration
  • Neuroprotection
  • NR2C subunit

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Fingerprint Dive into the research topics of 'Group-I metabotropic glutamate receptors: Hypotheses to explain their dual role in neurotoxicity and neuroprotection'. Together they form a unique fingerprint.

Cite this