TY - JOUR
T1 - The GluR2 (GluR-B) hypothesis
T2 - Ca2+-permeable AMPA receptors in neurological disorders
AU - Pellegrini-Giampietro, Domenico E.
AU - Gorter, Jan A.
AU - Bennett, Michael V.L.
AU - Zukin, R. Suzanne
N1 - Funding Information:
We thank Flavio Moroni, Thoralf Opitz and Ricardo C. Araneda for helpful comments on this manuscript. We are grateful to Howard S. Ying and Dennis W. Choi for permission to quote unpublished data. This work was supported in part by an Italian Government grant (MURST/PNR Neurobiology) to D.E.P-G. and by National Institutes of Health Grants (NS 20752 to R.S.Z. and NS 07412 to M.V.L.B.). M.V.L.B. is the Sylvia and Robert Olnick Professor of Neuroscience.
PY - 1997/10/1
Y1 - 1997/10/1
N2 - The abnormal influx of Ca2+ through glutamate receptor channels is thought to contribute to the loss of neurons associated with a number of brain disorders. Until recently, the NMDA receptor was the only glutamate receptor known to be Ca2+-permeable. It is now well established that AMPA receptors exist not only in Ca2+-impermeable but also in Ca2+-permeable forms. AMPA receptors are encoded by four genes designated gluRl (gluR-A) through gluR4 (gluR-D). The presence of the gluR2 subunit renders heteromeric AMPA receptor assemblies Ca2+-impermeable. Recent studies involving animal models of transient forebrain ischemia and epilepsy show that gluR2 mRNA is downregulated in vulnerable neurons. These observations suggest that downregulation of gluR2 gene expression may serve as a 'molecular switch' leading to the formation of Ca2+-permeable AMPA receptors and enhanced toxicity of endogenous glutamate following a neurological insult.
AB - The abnormal influx of Ca2+ through glutamate receptor channels is thought to contribute to the loss of neurons associated with a number of brain disorders. Until recently, the NMDA receptor was the only glutamate receptor known to be Ca2+-permeable. It is now well established that AMPA receptors exist not only in Ca2+-impermeable but also in Ca2+-permeable forms. AMPA receptors are encoded by four genes designated gluRl (gluR-A) through gluR4 (gluR-D). The presence of the gluR2 subunit renders heteromeric AMPA receptor assemblies Ca2+-impermeable. Recent studies involving animal models of transient forebrain ischemia and epilepsy show that gluR2 mRNA is downregulated in vulnerable neurons. These observations suggest that downregulation of gluR2 gene expression may serve as a 'molecular switch' leading to the formation of Ca2+-permeable AMPA receptors and enhanced toxicity of endogenous glutamate following a neurological insult.
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U2 - 10.1016/S0166-2236(97)01100-4
DO - 10.1016/S0166-2236(97)01100-4
M3 - Article
C2 - 9347614
AN - SCOPUS:0030763923
SN - 0166-2236
VL - 20
SP - 464
EP - 470
JO - Trends in Neurosciences
JF - Trends in Neurosciences
IS - 10
ER -