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The Role of Uric Acid as an Antioxidant in Selected Neurodegenerative Disease Pathogenesis: A Short Review

T Settle and H Klandorf

Uric acid, a potent antioxidant for humans, birds, reptiles, and some primate species, is the end-product of purine degradation that is formed in the xanthine/hypoxanthine reactions catalyzed by xanthine oxidase. Associated with the evolutionary loss of urate oxidase (the enzyme that oxidizes uric acid resulting in the formation of allantoin) and resulting increase in concentrations of uric acid is a prolonged life span. Uric acid is known to scavenge peroxynitrite and other free radicals that can cause an imbalance of oxidants leading to oxidative stress. Uric acid also has a role in protecting DNA from single-strand breaks caused by free radicals in the body leading to a protective effect in neurodegenerative diseases. The brain is particularly vulnerable to oxidative stress as it is considered an ‘expensive tissue’ with a particularly high metabolic rate and comparatively increased utilization of oxygen. Brain tissue is also high in unsaturated lipids, which makes it more susceptible to free radical damage. Oxidative stress is thus linked to the pathogenesis of neurodegenerative diseases and also ischemic brain injury. In this review, we summarize the function of uric acid in alleviating oxidative damage and providing protection to neural cells during injury and disease.