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

被引:145
作者
Nicoletti, F
Bruno, V
Catania, MV
Battaglia, G
Copani, A
Barbagallo, G
Ceña, V
Sanchez-Prieto, J
Spano, PF
Pizzi, M
机构
[1] Univ Catania, Dept Pharmaceut Sci, Pharmacol Sect, I-95125 Catania, Italy
[2] IMN Neuromed, Pozzilli, Italy
[3] CNR, IBFSNC, Catania, Italy
[4] Catania Univ, Dept Chem Sci, Catania, Italy
[5] Dept Pharmacol & Therapeut, Alicante, Spain
[6] Univ Complutense, Fac Vet, Dept Bioquim, E-28040 Madrid, Spain
[7] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy
关键词
group-I mGlu receptors; neurodegeneration; neuroprotection; NR2C subunit; 'functional switch'; astrocytes;
D O I
10.1016/S0028-3908(99)00102-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1477 / 1484
页数:8
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