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This review explores the essential roles of purine metabolism including the catabolic product, uric acid, in the development of dopaminergic neurons of the substantia nigra pars compacta. The high energy requirements of the substantia nigra pars compacta alongside necessary purinergic neurotransmission and the influence of oxidative stress during development makes these neurons uniquely susceptible to changes in purine metabolism. Uric acid's role as a central nervous system antioxidant may help to ameliorate these effects in utero. Understanding the mechanisms by which purines and uric acid influence development of the substantia nigra pars compacta can help further explain neurologic consequences of inborn errors of purine metabolism, such as Lesch-Nyhan disease.
Mileti et al. (Tue,) studied this question.