The Fundamental Role in Cellular Protection

• Superoxide dismutase (SOD) is a crucial antioxidant enzyme that combats oxidative stress.
• Catalyzes the conversion of superoxide radicals (O2•-) into hydrogen peroxide (H2O2) and molecular oxygen (O2).
• Counteracts reactive oxygen species (ROS), formed during cellular metabolism.
• Present in almost all cells, prevents oxidative damage that could lead to diseases and aging.

Types and Distribution in Living Systems

• Three forms of SOD found in mammals:
• SOD1 (Cu/Zn-SOD): Located in the cytosol, contains copper and zinc.
• SOD2 (Mn-SOD): Located in the mitochondrial matrix, uses manganese.
• SOD3 (EC-SOD): Located in the extracellular region, contains copper and zinc.
• Free radicals are neutralized in various cellular locations and tissues, providing extensive protection.

Mechanisms of Action and Cellular Protection

• SOD mechanism of action involves a two-step process, fluctuating between reducing and oxidizing the superoxide anion.
• Metal cofactor at the active site catalyzes the reduction of two superoxide ions to form hydrogen peroxide and oxygen.
• Reaction occurs at a rapid rate, making SOD one of the most effective enzymes.
• Formed hydrogen peroxide is neutralized by other antioxidants like catalase and glutathione peroxidase.

Clinical Significance and Disease Association

• Dysregulation of SOD function or expression involved in various diseases.
• Defects in the SOD1 gene cause familial amyotrophic lateral sclerosis (ALS), a fatal disease.
• Low SOD levels associated with cardiovascular diseases, cancer, diabetes, and neurodegenerative diseases (Alzheimer’s, Parkinson’s).
• Oxidative stress due to decreased SOD activity involved in aging and age-related diseases.
• Growing concern on therapeutic management of SOD activity or development of SOD mimetics for disease treatment.

Therapeutic Applications and Future Perspectives

• Research conducted on SOD's therapeutic uses in medicine and healthcare.
• Direct SOD administration effective against inflammation, ischaemia/reperfusion injury, and radiation damage.
• Issues like instability and low cellular uptake led to the creation of SOD mimetics.
• SOD mimetics provide SOD-like protection against oxidative damage, with benefits such as enhanced stability, tissue targeting, and bioavailability.