Neurotherapeutics

, Volume 14, Issue 1, pp 148–153

Urate as a Marker of Risk and Progression of Neurodegenerative Disease

Review

DOI: 10.1007/s13311-016-0497-4

Cite this article as:
Paganoni, S. & Schwarzschild, M.A. Neurotherapeutics (2017) 14: 148. doi:10.1007/s13311-016-0497-4

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 Risk Prognosis Inosine Oxidative stress 

Supplementary material

13311_2016_497_MOESM1_ESM.pdf (1.2 mb)
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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2016

Authors and Affiliations

  1. 1.Harvard Medical School, Department of NeurologyMassachusetts General HospitalBostonUSA
  2. 2.Department of Physical Medicine and RehabilitationSpaulding Rehabilitation HospitalBostonUSA
  3. 3.VA Boston Healthcare SystemBostonUSA
  4. 4.MassGeneral Institute for Neurodegenerative Disease (MIND)BostonUSA