Disruption of the GluR2-NSF interaction protects primary hippocampal neurons from ischemic stress

Molecular and Cellular Neurosciences
G S RalphJ B Uney

Abstract

A specific interaction between the AMPA receptor subunits GluR2 and GluR3 and the fusion protein NSF has recently been identified. Disruption of this interaction by adenoviral-mediated expression of a peptide (pep2m) corresponding to the NSF-binding region of GluR2 results in a dramatic reduction in surface expression of AMPA receptors in primary hippocampal neurons. Here we report that expression of pep2m from a recently developed neuronal-specific adenoviral system gave significant neuroprotection to primary CA1-CA3 hippocampal neurons following stimulation with kainate (KA) and this was accompanied by a reduction in Ca(2+) influx. Protection was also observed following glucose deprivation and exposure to ischemic buffer in the absence of any NMDA receptor antagonists. These results provide strong evidence that AMPA receptors play a direct role in mediating postischemic neurotoxicity.

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Citations

Mar 8, 2006·The European Journal of Neuroscience·Patrice QuintanaDominique Muller
Nov 16, 2004·Experimental Physiology·Youn-Bok LeeJames B Uney
Dec 7, 2014·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Yao QuXing-Zhi Li
Feb 22, 2003·Molecular and Cellular Neurosciences·Hiang Khoon TanJames B Uney
Mar 24, 2004·Journal of Structural Biology·Sidney W Whiteheart, Elena A Matveeva

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