Tat-NR2B9c Prevents Excitotoxic Neuronal Superoxide Production. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Chen, Yanting; Brennan-Minnella, Angela M; Sheth, Sunil; El-Benna, Jamel; Swanson, Raymond A
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 35:Issue 5(2015)
• Page Start: 739
• Page End: 742
• Publication Date: 2015-05
• Subjects: DNA damage; -- glutamate; -- ischemia; -- nitric oxide; -- oxidative stress; -- stroke; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2015.16
• Languages: English
• ISSNs: 0271-678X

Abstract

The Tat-NR2B9c peptide has shown clinical efficacy as a neuroprotective agent in acute stroke. Tat-NR2B9c is designed to prevent nitric oxide (NO) production by preventing postsynaptic density protein 95 (PSD-95) binding to N -methyl- D -aspartate (NMDA) receptors and neuronal nitric oxide synthase; however, PSD-95 is a scaffolding protein that also couples NMDA receptors to other downstream effects. Here, using neuronal cultures, we show that Tat-NR2B9c also prevents NMDA-induced activation of neuronal NADPH oxidase, thereby blocking superoxide production. Given that both superoxide and NO are required for excitotoxic injury, the neuroprotective effect of Tat-NR2B9c may alternatively be attributable to uncoupling neuronal NADPH oxidase from NMDA receptor activation.