N -methyl-D-aspartate receptors (NMDARs) mediate ischemic brain damage but blocking them is deleterious because these receptors also mediate essential neuronal excitation. In October 25 Science, Michelle Aarts and colleagues at the Toronto Western Hospital Research Institute, Toronto, Canada, show that perturbing NMDA receptor interactions with postsynaptic density protein PSD-95 may have a therapeutic effect on ischemic brain damage without influencing neuronal transmission (Science, 298:846-850, October, 25, 2002).

Aarts et al. transduced neurons with peptides that disrupted the interaction of NMDARs with the postsynaptic density protein PSD-95.They observed that this procedure dissociated NMDARs from downstream neurotoxic signaling without blocking synaptic activity or calcium in ?ux. In addition, application of the peptides either before or 1 hour after an insult, protected cultured neurons from excitotoxicity, reduced focal ischemic brain damage in rats, and improved their neurological function.

"Efficacy after the insult onset suggests targeting of the NMDAR–PSD-95 interaction...

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