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

Nature Biotechnology
Antonio Ferrer-MontielM Montal

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

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Citations

Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·K K TaiM Montal
Nov 26, 2009·Brain Research Bulletin·Francisco J Sánchez-MartínJaime M Merino
Feb 12, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bruno P MeloniNeville W Knuckey
Sep 21, 2000·FEBS Letters·R Planells-CasesA V Ferrer-Montiel
Feb 25, 1999·International Journal of Geriatric Psychiatry·R CacabelosB Winblad
Mar 22, 2002·The Journal of Pharmacology and Experimental Therapeutics·Carmina MontoliuVicente Felipo
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Rosa Planells-CasesAntonio Ferrer-Montiel
Dec 14, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Bruno P MeloniDouglas J Cook
Jul 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gabriella MacDougallBruno P Meloni
Mar 20, 2019·Journal of Neuropathology and Experimental Neurology·Bruno P MeloniNeville W Knuckey
Apr 24, 2020·Current Therapeutic Research, Clinical and Experimental·Li Shan ChiuBruno P Meloni

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