TY - JOUR
T1 - Neuroprotective activity of metabotropic glutamate receptor ligands
AU - Flor, Peter J.
AU - Battaglia, Giuseppe
AU - Nicoletti, Ferdinando
AU - Gasparini, Fabrizio
AU - Bruno, Valeria
PY - 2002
Y1 - 2002
N2 - Metabotropic glutamate receptors form a family of currently eight subtypes (mGluR1-8), subdivided into three groups (I-III). Activation of group-II (mGluR2 and -3) or group-III metabotropic glutamate receptors (mGluR4, -6, -7 and -8) has been established to be neuroprotective in vitro and in vivo. In contrast, group-I mGluRs (mGluR1 and -5) need to be antagonized in order to evoke protection. Initially, all neuroprotective mGluR ligands were analogues of L-glutamate. Those compounds were valuable to demonstrate protection in vitro, but showed limited applicability in animal models, particularly in chronic tests, due to low blood-brain-barrier penetration. Recently, systemically active and more potent and selective ligands became available, e.g., the group-II mGluR agonists LY354740 and LY379268 or group-I antagonists like MPEP (mGluR5-selective) and BAY36-7620 (mGluR1-selective). This new generation of pharmacological agents allows a more stringent assessment of the role of individual mGluR-subtypes or groups of receptors in various nervous system disorders, including ischaemia-induced brain damage, traumatic brain injury, Huntington s and Parkinson s-like pathology or epilepsy. Moreover, the use of genetically modified animals (e.g., knock-out mice) is starting to shed light on specific functions of mGluR-subtypes in experimental neuropathologies.
AB - Metabotropic glutamate receptors form a family of currently eight subtypes (mGluR1-8), subdivided into three groups (I-III). Activation of group-II (mGluR2 and -3) or group-III metabotropic glutamate receptors (mGluR4, -6, -7 and -8) has been established to be neuroprotective in vitro and in vivo. In contrast, group-I mGluRs (mGluR1 and -5) need to be antagonized in order to evoke protection. Initially, all neuroprotective mGluR ligands were analogues of L-glutamate. Those compounds were valuable to demonstrate protection in vitro, but showed limited applicability in animal models, particularly in chronic tests, due to low blood-brain-barrier penetration. Recently, systemically active and more potent and selective ligands became available, e.g., the group-II mGluR agonists LY354740 and LY379268 or group-I antagonists like MPEP (mGluR5-selective) and BAY36-7620 (mGluR1-selective). This new generation of pharmacological agents allows a more stringent assessment of the role of individual mGluR-subtypes or groups of receptors in various nervous system disorders, including ischaemia-induced brain damage, traumatic brain injury, Huntington s and Parkinson s-like pathology or epilepsy. Moreover, the use of genetically modified animals (e.g., knock-out mice) is starting to shed light on specific functions of mGluR-subtypes in experimental neuropathologies.
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M3 - Article
C2 - 12575822
AN - SCOPUS:0345894319
VL - 513
SP - 197
EP - 223
JO - Advances in Experimental Medicine and Biology
JF - Advances in Experimental Medicine and Biology
SN - 0065-2598
ER -