MicroRNA-223 is neuroprotective by targeting glutamate receptors

• DOI: 10.1073/pnas.1121288109
• Publication Date: 2012-10-30T05:46:22Z
• Authors: Maged M. Harraz; Stephen M. Eacker; Xueqing Wang; Ted M. Dawson; Valina L. Dawson
• Keywords: Excitotoxicity; Long-term depression

Stroke is a major cause of mortality and morbidity worldwide. Extracellular glutamate accumulation leading to overstimulation the ionotropic receptors mediates neuronal injury in stroke neurodegenerative disorders. Here we show that miR-223 controls response by regulating functional expression receptor subunits GluR2 NR2B brain. Overexpression lowers levels targeting 3′-UTR target sites (TSs) NR2B, inhibits NMDA-induced calcium influx hippocampal neurons, protects brain from cell death following transient global ischemia excitotoxic injury. MiR-223 deficiency results higher GluR2, enhanced influx, increased miniature excitatory postsynaptic currents neurons. In addition, absence leads contextual, but not cued memory deficits excitotoxicity. These data identify as regulator suggest therapeutic role for other