Plasma urate and risk of Parkinson's disease.

Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA.
American Journal of Epidemiology (Impact Factor: 4.98). 10/2007; 166(5):561-7. DOI: 10.1093/aje/kwm127
Source: PubMed

ABSTRACT Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease, the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort comprising over 18,000 men who provided blood samples in 1993-1995. Eighty-four incident cases of Parkinson's disease were diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection. Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression. The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caffeine, the rate ratio of Parkinson's disease for the highest quartile of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; p(trend) = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection (rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; p(trend) = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's disease.

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    ABSTRACT: Epidemiological studies have indicated an inverse association between high uricemia and incidence of Parkinson's disease (PD). To investigate the link between endogenous urate and neurotoxic changes involving the dopaminergic nigrostriatal system, this study evaluated the modifications in the striatal urate levels in two models of PD. To this end, a partial dopaminergic degeneration was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice, while a severe dopaminergic degeneration was elicited by unilateral medial forebrain bundle infusion of 6-hydroxydopamine (6-OHDA) in rats. Urate levels were measured by in vivo microdialysis at 7 or 14 days from toxin exposure. The results obtained demonstrated higher urate levels in the dopamine (DA)-denervated striatum of 6-OHDA-lesioned rats compared with the intact striatum. Moreover, an inverse correlation between urate and DA levels was observed in the same area. In contrast, only a trend to significant increase in striatal urate was observed in MPTP-treated mice. These results demonstrate that a damage to the dopaminergic nigrostriatal system elevates the striatal levels of urate, and suggest that this could be an endogenous compensatory mechanism to attenuate dopaminergic neurodegeneration. This finding may be important in light of the epidemiological and preclinical evidences that indicate a link between urate and development of PD. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2014; 131(3):284-289. DOI:10.1111/jnc.12809 · 4.24 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. It is now clear that genetic susceptibility and environmental factors play a role in disease etiology and progression. Because environmental factors are involved with the majority of the cases of PD, it is important to understand the role nutrition plays in both neuroprotection and neurodegeneration. Recent epidemiological studies have revealed the promise of some nutrients in reducing the risk of PD. In contrast, other nutrients may be involved with the etiology of neurodegeneration or exacerbate disease progression. This review summarizes the studies that have addressed these issues and describes in detail the nutrients and their putative mechanisms of action in PD.
    Frontiers in Aging Neuroscience 03/2014; 6:36. DOI:10.3389/fnagi.2014.00036 · 2.84 Impact Factor


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