Tat-NR2B9c prevents excitotoxic neuronal superoxide production |
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| Authors: | Yanting Chen Angela M Brennan-Minnella Sunil Sheth Jamel El-Benna Raymond A Swanson |
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| Institution: | 1.Department of Neurology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, PR China;2.Department of Neurology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, California, USA;3.INSERM, U1149, CNRS-ERL8252, Centre de Recherche sur l''Inflammation Paris,, Paris, France;4.Laboratoire d''Excellence Inflamex, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat,, Paris, France |
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| 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. |
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| Keywords: | DNA damage glutamate ischemia nitric oxide oxidative stress stroke |
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