Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death
Article
Ferrer-Montiel, AV, Merino, JM, Blondelle, SE et al. (1998). Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death
. NATURE BIOTECHNOLOGY, 16(3), 286-291. 10.1038/nbt0398-286
Ferrer-Montiel, AV, Merino, JM, Blondelle, SE et al. (1998). Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death
. NATURE BIOTECHNOLOGY, 16(3), 286-291. 10.1038/nbt0398-286
Excitotoxic neuronal death, associated with neurodegeneration and stroke, is triggered primarily by massive Ca2+ influx arising from overactivation of glutamate receptor channels of the N-methyl-D-aspartate (NMDA) subtype. To search for channel blockers, synthetic combinatorial libraries were assayed for block of agonist-evoked currents by the human NR1- NR2A NMDA receptor subunits expressed in amphibian oocytes. A set of arginine-rich hexapeptides selectively blocked the NMDA receptor channel with IC50 approximately 100 nM, a potency similar to clinically tolerated blockers such as memantine, and only marginally blocked on non-NMDA glutamate receptor. These peptides prevent neuronal cell death elicited by an excitotoxic insult on hippocampal cultures.
