Oxidative Stress: Molecular Mechanisms, Diseases, and Therapeutic Targets

Although the physiological level of reactive oxygen species (ROS) is crucial for governing life processes through redox signaling, the excessive accumulation of ROS can contribute to biomolecular damage and pathological state, namely, oxidative stress. This review systematically summarizes the molecular mechanisms underlying the dynamic equilibrium of cellular redox state, including the intracellular sources of ROS and the multilayered antioxidant defense network. When ROS production exceeds the regulatory limits of the antioxidant system, excessive ROS will act on a series of molecular targets and participate in the pathogenesis of diseases. Therapeutic targeting of the redox balance is regarded as an effective strategy for treating oxidative stress-related diseases, such as supplementation of direct antioxidants and enhancement of endogenous antioxidant defense network. Nevertheless, clinical trials that attempt to delay the onset or progression of such diseases are mostly negative. This review discusses the challenges encountered in the clinical application of antioxidant therapy and highlights the opportunities brought by novel technologies such as intelligent drug delivery system and personalized medicine. By adopting these new technologies, it is expected to overcome the limitations of traditional antioxidant therapy.