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: Yanting Chen, Angela M Brennan-Minnella, Sunil Sheth, Jamel El-Benna, Raymond A Swanson
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 35 Issue 5 Pg. 739-42 (May 2015) ISSN: 1559-7016 [Electronic] United States
• PMID: 25669908 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Disks Large Homolog 4 Protein
• Dlg4 protein, mouse
• Membrane Proteins
• Neuroprotective Agents
• Peptides
• Receptors, N-Methyl-D-Aspartate
• Superoxides
• Nitric Oxide
• Tat-NR2B9c
• NADPH Oxidases
• Guanylate Kinases

Topics

• Animals
• Cells, Cultured
• Disks Large Homolog 4 Protein
• Guanylate Kinases (metabolism)
• Membrane Proteins (metabolism)
• Mice
• NADPH Oxidases (metabolism)
• Neurons (metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide (biosynthesis)
• Peptides (pharmacology)
• Protein Binding
• Receptors, N-Methyl-D-Aspartate (metabolism)
• Superoxides (metabolism)