Publication date: Jul 13, 2023

Inflammasomes are multimeric complexes that, as part of the innate immune response, sense a wide range of pathogenic and sterile stimuli. They consist of three components, namely a sensor protein, an adaptor, and pro-caspase-1 that, once activated, result in secretion of pro-inflammatory interleukin-1β (IL-1β) and IL-18 and, eventually, in a gasdermin D-dependent lytic cell death called pyroptosis. Since their discovery 20 years ago, the molecular mechanisms underlying the regulation of inflammasomes have been extensively studied. Oxidative stress appears as a major contributor to modulate inflammasomes, especially NLRP3 as well as NLRP1, NLRP6 and NLRC4. Growing evidence support the idea that the positive feedback between redox imbalance and inflammasome-driven inflammation fuels an OxInflammatory state in a variety of human pathologies. The current knowledge about the redox signaling pathways involved in inflammasomes activation and functions are here highlighted. In addition, we discuss the role of this complex molecular network interaction in the onset and progression of pathological conditions including neurological and metabolic diseases as well as skin disorders, also with an insight on COVID-19 related pathology. Finally, the therapeutic strategies able to mitigate the redox-mediated inflammasome activation with synthetic and natural compounds as well as by acting on inflammasome-related posttranslational modifications and microRNAs are also addressed. Further investigations leading to a deeper understanding of the reciprocal interaction between inflammasomes and ROS will help to identify other molecular targets for modulating their hyperactivated state and to design novel therapeutics for chronic OxInflammatory conditions.

Semantics

Original Article