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

cited authors

  • Ferrer-Montiel, AV; Merino, JM; Blondelle, SE; Perez-Payà, E; Houghten, RA; Montal, M

abstract

  • 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.

publication date

  • March 28, 1998

published in

Digital Object Identifier (DOI)

start page

  • 286

end page

  • 291

volume

  • 16

issue

  • 3