title: Urate as a Marker of Risk and Progression of Neurodegenerative Disease.
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.
authors.affiliation: Harvard Medical School, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. spaganoni@partners.org.|Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Boston, MA, USA. spaganoni@partners.org.|VA Boston Healthcare System, Boston, MA, USA. spaganoni@partners.org.
authors.forename: Sabrina
authors.identifier: 0000-0003-0505-1168
authors.initials: S
authors.lastname: Paganoni
authors.affiliation: Harvard Medical School, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.|MassGeneral Institute for Neurodegenerative Disease (MIND), Boston, MA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Schwarzschild
mesh_terms: D000818:Animals; D015415:Biomarkers; D002986:Clinical Trials as Topic; D018450:Disease Progression; D006801:Humans; D019636:Neurodegenerative Diseases / Q000175:diagnosis* / Q000378:metabolism*; D010300:Parkinson Disease / Q000175:diagnosis / Q000378:metabolism; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D014527:Uric Acid
keywords: Biomarker; Inosine; Oxidative stress; Prognosis; Risk