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Current Topics in Medicinal Chemistry 2015

The Role of Uric Acid and Methyl Derivatives in the Prevention of Age-Related Neurodegenerative Disorders.

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Roy G Cutler
Simonetta Camandola
Kelli F Malott
Maria A Edelhauser
Mark P Mattson

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High uric acid (UA levels have been correlated with a reduced risk of many neurodegenerative diseases through mechanisms involving chelating Fenton reaction transitional metals, antioxidant quenching of superoxide and hydroxyl free radicals, and as an electron donor that increases antioxidant enzyme activity (e.g. SOD. However, the clinical usefulness of UA is limited by its' low water solubility and propensity to form inflammatory crystals at hyperuricemic levels. This review focuses on the role of UA in neuroprotection, as well as potential strategies aimed at increasing UA levels in the soluble range, and the potential therapeutic use of more water-soluble methyl-UA derivatives from the natural catabolic end-products of dietary caffeine, theophylline, and theobromine.

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