cGAS-STING signaling in pollution-induced toxicity: mechanism and relieving medication.

Abstract

Environmental pollutants have long been a major threat to human health, and long-term or high-concentration exposure can trigger acute or chronic diseases. These hazards often mediate tissue dysfunction and drive disease progression by inducing cell senescence and cell death (including apoptosis, pyroptosis, and ferroptosis). In recent years, the cGAS-STING signaling axis, as the core pathway for sensing cytosolic DNA, has received extensive attention and research. Its activation can promote the expression of type I interferons and inflammatory factors, playing an important role in immune defense such as anti-infection and anti-tumor. Notably, senescence-associated DNA leakage and mitochondrial dysfunction provide persistent ligands for cGAS, thereby establishing a self-sustaining cGAS-STING-driven inflammatory loop that exacerbates aging-related pathologies. However, research on the link between pollutants and the cGAS-STING pathway is still limited. In this review, we describe in detail the mechanism of action of the cGAS-STING pathway, focusing on how various pollutants (including heavy metals, air pollutants, and industrial chemicals) interfere with the cGAS-STING pathway, leading to cell damage and disease occurrence. Finally, we also list some drugs that can alleviate the impact of pollutants on the cGAS-STING signaling axis. Overall, this review aims to provide a theoretical basis for a deeper understanding of pollutant toxicity mechanisms and for developing intervention strategies targeting the cGAS-STING pathway.