6533b82cfe1ef96bd128f65e

RESEARCH PRODUCT

Selected peptides targeted to the NMDA receptor channel protect neurons from excitotoxic death

Enrique Pérez-payáEnrique Pérez-payáMauricio MontalRichard A. HoughtenAntonio Ferrer-montielJaime M. MerinoSylvie E. Blondelle

subject

medicine.medical_specialtyXenopusDrug Evaluation PreclinicalBiomedical EngineeringBioengineeringHippocampal formationBiologyPharmacologyArginineBinding CompetitiveHippocampusReceptors N-Methyl-D-AspartateApplied Microbiology and BiotechnologySubstrate SpecificityInternal medicinemedicineAnimalsHumansChannel blockerReceptorNeuronsCell DeathNeurodegenerationGlutamate receptorMemantinemedicine.diseaseRatsEndocrinologymedicine.anatomical_structurenervous systemDrug DesignOocytesMolecular MedicineNMDA receptorFemaleNeuronPeptidesBiotechnologymedicine.drug

description

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 receptors. These peptides prevent neuronal cell death elicited by an excitotoxic insult on hippocampal cultures.

yearjournalcountryeditionlanguage
1998-03-01Nature Biotechnology
https://doi.org/10.1038/nbt0398-286