title: Tat-NR2B9c prevents excitotoxic neuronal superoxide production.
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.
authors: 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.
authors: Yanting
authors: Y
authors: Chen
authors: Department of Neurology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, California, USA.
authors: Angela M
authors: AM
authors: Brennan-Minnella
authors: Department of Neurology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, California, USA.
authors: Sunil
authors: S
authors: Sheth
authors: 1] INSERM, U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation Paris, Paris, France [2] Laboratoire d'Excellence Inflamex, Université Paris Diderot, Sorbonne Paris Cité, Site Xavier Bichat, Paris, France.
authors: Jamel
authors: J
authors: El-Benna
authors: Department of Neurology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, California, USA.
authors: Raymond A
authors: RA
authors: Swanson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; D013481:Superoxides; D009569:Nitric Oxide; C542597:Tat-NR2B9c; D019255:NADPH Oxidases; D051528:Guanylate Kinases