Article by Biophysics Researchers Selected as Antioxidants Cover Story

Matea Juric, second-year medical student at MCW; Jacek Zielonka, PhD, assistant professor of biophysics at MCW; and Varun Rawat, PhD, Radhika Amaradhi, PhD, and Thota Ganesh, PhD, at Emory University School of Medicine published an article titled “Novel NADPH Oxidase-2 Inhibitors as Potential Anti-Inflammatory and Neuroprotective Agents,” in Antioxidants. The article was selected as the journal’s September 2023 (Volume 12, Issue 9) cover story.

In the article, the co-authors discuss their work to develop novel, brain permeable Nox2 inhibitors with neuroprotective potential. The oxidative burst produced by NADPH oxidase enzymes within macrophages and neutrophils incites a potent bactericidal effect in response to invading pathogens. Aberrant activation of these enzymes has been implicated in a variety of diseases, including neurodegeneration. In this work, we developed a novel, brain-permeable NOX inhibitor, TG15-132, as a potential neuroprotective agent. TG15-132 demonstrated potent inhibition of Nox2 activity in neutrophil-like cells. Extended treatment with TG15-132 in human macrophages down-regulated expression of genes encoding Nox2 subunits and several pro-inflammatory cytokines. In rodent models, TG15-132 exhibited a long plasma half-life and a high brain-to-blood level ratio. Therefore, TG15-132 may serve as a promising neuroprotective agent.