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Review
. 2017 Jan;14(1):148-153.
doi: 10.1007/s13311-016-0497-4.

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Sabrina Paganoni  1   2   3 , Michael A Schwarzschild  4   5
Affiliations
Review

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Sabrina Paganoni et al. Neurotherapeutics. 2017 Jan.

Abstract

Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases. Most importantly, beyond its role as a molecular predictor of disease risk and progression, urate may constitute a novel therapeutic target. Indeed, clinical trials of urate elevation in PD and amyotrophic lateral sclerosis are testing the impact of raising peripheral urate levels on disease outcomes. These studies will contribute to unraveling the neuroprotective potential of urate in human pathology. In parallel, preclinical experiments are deepening our understanding of the molecular pathways that underpin urate's activities. Altogether, these efforts will bring about new insights into the translational potential of urate, its determinants, and its targets and their relevance to neurodegeneration.

Keywords: Biomarker; Inosine; Oxidative stress; Prognosis; Risk.

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Figures

Fig. 1
Fig. 1
Translational potential of urate across neurologic diseases. Epidemiologic and laboratory evidence support a neuroprotective role of urate. Urate elevation has been employed in early clinical trials and has rapidly advanced to phase III testing in Parkinson’s disease (SURE-PD3 trial; NCT02642393; open to enrollment at the time of this publication). Enrollment for SURE-ALS2 is scheduled to begin in early 2017. ALS = amyotrophic lateral sclerosis; PD = Parkinson’s disease; SURE-ALS2 = safety of urate elevation in ALS, phase II; SURE-PD = safety of urate elevation in PD; SURE-PD3 = study of urate elevation in PD, phase III
Fig. 2
Fig. 2
Biomarker properties of urate across the timeline of Parkinson’s disease (PD). Several studies support urate or its determinants (dietary or genetic) as a biomarker of PD at different points in the PD stage, which refers to Hoehn and Yahr scale stage
See this image and copyright information in PMC

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