Products Cited in Publications Worldwide Sex-Dependent Modulation of Nox2-Mediated Oxidative Stress in Epilepsy

Sex-Dependent Modulation of Nox2-Mediated Oxidative Stress in Epilepsy

Singh, Prince Kumar; Maurya, Shweta; Saadi, Aseel; Zhang, Taige; Lieb, Andreas; Shekh-Ahmad, Tawfeeq

DOI:

Abstract

NOX2-driven reactive oxygen species mediated oxidative stress and neuroinflammation play a critical role in the pathophysiology of neurological disorders such as epilepsy. However, sex-dependent differences in the regulation of NOX2 associated oxidative stress and neuroinflammation and therapeutic targeting remain largely unexplored. Although various NOX inhibitors have been investigated, many have poor specificity, toxicity, and lack sustained efficacy. There is an urgent need for selective NOX2 inhibitors capable of mitigating oxidative stress and driven neuroinflammation while accounting for their sex-dependent responses. In this study, we investigated the therapeutic potential of GSK2795039, a selective NOX2 inhibitor, in reducing seizure burden, oxidative stress-mediated neuronal damage, and cognitive impairment in a sex-specific manner. GSK2795039 target NOX2 and associated oxidative stress-driven neuroinflammation efficiently in male over female rats following status epilepticus. However, males exhibited a more pronounced therapeutic response, with greater reductions in seizure and interictal spiking frequency, and neuronal loss, as well as improved cognitive outcomes. The comparatively weaker response in females suggests a reliance on alternative antioxidant and neuroprotective pathways. Our findings underscore the importance of considering sex as a biological variable in epilepsy treatment and highlight GSK2795039 as a promising NOX2-targeted therapy with differential efficacy based on sex-dependent redox homeostasis and inflammatory regulation.

Keywords

GSK2795039 ; NADPH Oxidase 2 ; Epileptogenesis ; Kainic Acid ; Oxidative stress

Purchased from AmBeed

GSK2795039

A2519631415925-18-697%

GSK2795039

162.0/25mg

Detail