Oxidative stress and antioxidant enzyme pathways

Oxidative stress and antioxidant enzyme pathways represent a complex network of biochemical processes dedicated to maintaining cellular redox homeostasis (Sies et al., 2017). This system involves key enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx), which neutralize reactive oxygen species (ROS) like superoxide and hydrogen peroxide to prevent damage to lipids, proteins, and DNA (Pizzino et al., 2017). The pathway is primarily regulated by the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which coordinates the expression of numerous cytoprotective genes in response to oxidative challenge (He et al., 2020). Dysregulation of these pathways is a hallmark of various chronic conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer (Forman and Zhang, 2021). Pharmacological intervention typically aims to either directly scavenge ROS or, more effectively, activate endogenous antioxidant defenses through Nrf2 modulation, as seen with drugs like dimethyl fumarate. However, therapeutic development is challenged by the dual role of ROS as both damaging agents and essential signaling molecules, necessitating precise control to avoid disrupting normal physiological functions or inadvertently protecting malignant cells (Pizzino et al., 2017).

Other names

Redox signaling pathwaysAntioxidant defense systemReactive oxygen species (ROS) scavenging systemNrf2-ARE signaling axis

Pharmacological modulation typically involves the activation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which binds to Antioxidant Response Elements (ARE) to induce the expression of phase II antioxidant enzymes (e.g., SOD, CAT, GPx), or the use of direct ROS scavengers and enzyme mimics to restore redox balance (He et al., 2020; Pizzino et al., 2017).