ROS-Driven STAT1 S-Glutathionylation Sustains IFNγ Signaling and Pro-Inflammatory Microglial Polarization.

ABSTRACT: Oxidative stress is a major driver of neuroinflammation, yet the molecular redox mechanisms that shape microglial activation remain incompletely defined. Among reversible redox modifications, protein S-glutathionylation has emerged as a key regulator of signaling cascades under conditions of elevated Reactive Oxygen Species (ROS). While IFNγ is known to activate STAT1 and promote a pro-inflammatory microglial phenotype, the contribution of oxidative stress to this process is poorly understood. Here, we investigated the interplay between ROS and STAT1 signaling in IFNγ-stimulated microglial cells. We demonstrate that ROS not only enhance STAT1 phosphorylation but also promote its S-glutathionylation, a modification that sustains STAT1 transcriptional activity. This dual regulation leads to

SUBMITTER: Brattini M 

PROVIDER: S-EPMC12729941 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature