Recent findings have provided insights into the pathophysiology and mechanisms of ischemic stroke, complementing the traditional glutamate hypothesis: the molecular interaction between PSD95 and GluN2B has been identified as a culprit in stroke-mediated excitotoxicity, leading to the discovery of NA-1, a peptide that disrupts that interaction, as a potent neuroprotective agent for the treatment of acute stroke.
These data identify miR-223 as a major regulator of the expression of GluR2 and NR2B, and suggest a therapeutic role for miR-223 in stroke and other excitotoxic neuronal disorders.
We found that NR2A- and NR2B-containing NMDA receptor subtypes play differential roles in ischemic neuronal death and ischemic tolerance, suggesting attractive new strategies for the development of drugs for patients with stroke.