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Editorial |

Natural Oxidant Balance in Parkinson Disease

George Perry, PhD; Paula I. Moreira, PhD; Sandra L. Siedlak, BA; Akihiko Nunomura, MD; Xiongwei Zhu, PhD; Mark A. Smith, PhD
Arch Neurol. 2009;66(12):1445. doi:10.1001/archneurol.2009.261.
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More than a half century old and with a great array of supportive data, the Harmon Free Radical Theory of Aging has too often fallen short of the pivotal demonstration that oxidative stress underlies the biology of aging. While antioxidant nutrients are essential, increased supplementation during disease processes has yielded disappointing or even detrimental effects. Why, if the brain is so poorly protected from oxidants and the center of almost a quarter of the body's respiration, does increasing antioxidants not have benefit for Parkinson disease (PD), a condition in which oxidative stress has been amply demonstrated? The answer has come to the Parkinson Study Group (PSG) DATATOP Investigators,1 who show that low serum/cerebrospinal fluid levels of the natural antioxidant urate are a predictor of development of PD. In humans, instead of being further metabolized and excreted, urate is retained, and slowly excreted intact high levels of urate act as a stoichiometric sink for radicals. The high levels of urate maintained in humans not only predict risk of gout but also act as one of the key antioxidants. Antioxidant defenses are critical and, as such, are linked to pivotal metabolic pathways. Understanding oxidant balance does not encompass just the nutrients vitamins C and E and others but also the pathways linked to the reductant, chelation, compartmentation, and stress responses underlying cellular metabolism. The PSG DATATOP study implicates the changes in urate levels as pivotal in PD. We propose that regulation of the intricate web of oxidant responses protects the brain, whether one takes supplements or not. A surprise? Not really, considering that there is probably nothing more important to human survival than maintaining brain function. With the development of PD, increased oxidative stress is met by increased levels of antioxidants or, as this study suggests, individuals who have responded early through increased urate levels are protected from PD.

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