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Cited by 258

MicroRNA-223 is neuroprotective by targeting glutamate receptors

Harraz, Maged M., Eacker, Stephen M., Wang, Xueqing, Dawson, Ted M., Dawson, Valina L.·2012·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1121288109
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Abstract

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

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Authors
Harraz, M. M., Eacker, S. M., Wang, X., Dawson, T. M., & Dawson, V. L.
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2012-10-29
Volume
109
Issue
46
Pages
18962-18967
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1121288109
Cited by
258
References
2
Language
en

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