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 “,” 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.