Reactive oxygen species metabolism and oxidative stress pathways (ROS/Oxidative Stress Pathways)

Reactive oxygen species (ROS) metabolism and oxidative stress pathways encompass the biochemical processes responsible for the generation, neutralization, and signaling of reactive oxygen and nitrogen species within the cell [10, 14]. Under physiological conditions, ROS act as essential second messengers in signaling cascades that regulate cell growth, differentiation, and immune responses [13, 14]. However, an imbalance between ROS production and the capacity of antioxidant defense systems—such as superoxide dismutase (SOD), catalase, and the glutathione system—leads to oxidative stress, which causes damage to DNA, proteins, and lipids [1, 7, 14]. This state of oxidative stress is a hallmark of numerous pathologies, including cancer, neurodegenerative diseases, and cardiovascular disorders [3, 5, 14]. Therapeutic strategies targeting these pathways aim to restore redox homeostasis by either inhibiting ROS-generating enzymes like NADPH oxidase (NOX) or activating cytoprotective transcription factors such as Nrf2 [4, 16]. Drugs like dimethyl fumarate and bardoxolone methyl leverage these pathways to enhance endogenous antioxidant defenses [4, 5]. Conversely, in cancer therapy, some agents are designed to exacerbate oxidative stress to selectively induce apoptosis in tumor cells [3, 4]. Despite their potential, targeting these pathways remains challenging due to the dual role of ROS in both health and disease, where excessive suppression can interfere with vital physiological signaling [8, 10].

Other names

Oxidative stress responseRedox signalingROS homeostasisRedox metabolism

Modulation of redox balance through the activation of antioxidant transcription factors (e.g., Nrf2), inhibition of ROS-generating enzymes (e.g., NADPH oxidase, xanthine oxidase), or direct scavenging of reactive species [4, 14, 16].