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. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.
Group-I metabotropic glutamate receptors: hypotheses to explain their dual role in neurotoxicity and neuroprotection / Nicoletti, Ferdinando; Bruno, Valeria Maria Gloria; M. V., Catania; Battaglia, Giuseppe; A., Copani; G., Barbagallo; V., Cena; J., Sanchez Prieto; P. F., Spano; M., Pizzi. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 38:10(1999), pp. 1477-1484. (Intervento presentato al convegno 3rd International Meeting on Metabotropic Glutamate Receptors tenutosi a TAORMINA, ITALY nel SEP 19-24, 1999) [10.1016/s0028-3908(99)00102-1].
Group-I metabotropic glutamate receptors: hypotheses to explain their dual role in neurotoxicity and neuroprotection
NICOLETTI, Ferdinando;BRUNO, Valeria Maria Gloria;BATTAGLIA, Giuseppe;
1999
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. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
