Oxidative stress regulatory pathways

Oxidative stress regulatory pathways represent a sophisticated network of cellular mechanisms, most notably the Nrf2-KEAP1-ARE axis, dedicated to maintaining redox homeostasis by neutralizing reactive oxygen species (ROS) [1]. These pathways involve a variety of enzymes, such as superoxide dismutase (SOD), catalase, and glutathione peroxidase, which work in concert to prevent oxidative damage to cellular macromolecules [2]. Chronic oxidative stress is a fundamental driver of pathology in neurodegenerative diseases, cardiovascular conditions, and metabolic disorders, making these pathways attractive for therapeutic intervention [3]. Current pharmacological approaches include Nrf2 activators like dimethyl fumarate and omaveloxolone, which enhance the cell's endogenous antioxidant capacity [4]. However, drug development faces significant hurdles, including the potential for 'Nrf2 addiction' in tumors where the pathway promotes cancer cell survival and chemoresistance, as well as the difficulty in achieving precise redox modulation without disrupting essential physiological ROS signaling [5].

Other names

Antioxidant response element pathwayNrf2-Keap1 signaling pathwayRedox homeostasis pathwaysROS regulatory networkNFE2L2 pathway

Activation of the Nrf2-Keap1-ARE signaling axis to upregulate endogenous antioxidant enzymes or direct scavenging of reactive oxygen species.