The role and mechanism of the cGAS–STING pathway-mediated ROS in apoptosis and ferroptosis induced by manganese exposure

Environmental exposure to elevated manganese (Mn) levels is significantly associated with neurocognitive deficits, attracting widespread attention, yet its underlying mechanisms remain incompletely defined. Ferroptosis is recognized as a crucial contributor to cognitive impairments. Our study demonstrates that Mn exposure activates the cGAS–STING pathway, mediating reactive oxygen species (ROS) generation and subsequently inducing apoptosis and ferroptosis. Mechanistically, Mn-induced cGAS–STING activation promotes oxidative stress, characterized by increased ROS and malondialdehyde (MDA) production, alongside diminished glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities. Furthermore,…