How interactions between oxidized DNA and the NLRP3 inflammasome fuel inflammatory disease
Angela Lackner, Lemuel Leonidas, Alijah Macapagal, Hannah Lee, Reginald McNulty
Abstract
Recent discoveries have emphasized the critical role of oxidized DNA (ox-DNA) in inflammation and immune regulation. Produced during oxidative stress from infection or tissue damage, ox-DNA activates signaling pathways that drive the release of proinflammatory cytokines, specifically engaging the NLRP3 inflammasome, a key player in cytokine maturation and host defense. NLRP3 is increasingly implicated in inflammatory and autoimmune diseases, with ox-DNA recognized as a central activator of this inflammasome. This review examines the role of ox-DNA in inflammasome activation, its broader impact on inflammatory processes, and promising therapeutic approaches targeting ox-DNA through both immunological and structural lenses. These insights highlight ox-DNA's relevance in inflammation and offer potential avenues for the treatment of a range of immune-related disorders.