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Urate: a novel biomarker of Parkinson's disease risk, diagnosis and prognosis.

ABSTRACT: A growing number of studies have correlated higher urate levels with a lower risk of developing Parkinson's disease (PD) and with a favorable rate of disease progression, indicating that urate could be an important biomarker of the pathophysiology underlying PD. Dietary and genetic determinants of urate have also been linked to a reduced risk or delayed onset of PD. Based on the known antioxidant and metal complexing properties of urate, together with evidence for oxidative stress as a contributor to neurodegeneration in PD, urate may serve as an endogenous neuroprotectant that helps reduce the risk and rate of the disease. In this article we review the convergent biological, epidemiological and clinical data that identify urate as a promising biomarker of the risk, diagnosis and prognosis of PD.

SUBMITTER: Cipriani S

PROVIDER: S-EPMC3049925 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Urate: a novel biomarker of Parkinson's disease risk, diagnosis and prognosis.

Cipriani Sara S Chen Xiqun X Schwarzschild Michael A MA

Biomarkers in medicine 20101001 5

A growing number of studies have correlated higher urate levels with a lower risk of developing Parkinson's disease (PD) and with a favorable rate of disease progression, indicating that urate could be an important biomarker of the pathophysiology underlying PD. Dietary and genetic determinants of urate have also been linked to a reduced risk or delayed onset of PD. Based on the known antioxidant and metal complexing properties of urate, together with evidence for oxidative stress as a contribut ...[more]

PMID: 20945982

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Project description:In many cancers, cells undergo re-programming of metabolism, cell survival and anti-apoptotic defense strategies, with the proteins mediating this reprogramming representing potential biomarkers. Here, we searched for novel biomarker proteins in chronic lymphocytic leukemia (CLL) that can impact diagnosis, treatment and prognosis by comparing the protein expression profiles of peripheral blood mononuclear cells from CLL patients and healthy donors using specific antibodies, mass spectrometry and binary logistic regression analyses and other bioinformatics tools. Mass spectrometry (LC-HR-MS/MS) analysis identified 1,360 proteins whose expression levels were modified in CLL-derived lymphocytes. Some of these proteins were previously connected to different cancer types, including CLL, while four other highly expressed proteins were not previously reported to be associated with cancer, and here, for the first time, DDX46 and AK3 are linked to CLL. Down-regulation expression of two of these proteins resulted in cell growth inhibition. High DDX46 expression levels were associated with shorter survival of CLL patients and thus can serve as a prognosis marker. The proteins with modified expression include proteins involved in RNA splicing and translation and particularly mitochondrial proteins involved in apoptosis and metabolism. Thus, we focused on several metabolism- and apoptosis-modulating proteins, particularly on the voltage-dependent anion channel 1 (VDAC1), regulating both metabolism and apoptosis. Expression levels of Bcl-2, VDAC1, MAVS, AIF and SMAC/Diablo were markedly increased in CLL-derived lymphocytes. VDAC1 levels were highly correlated with the amount of CLL-cancerous CD19+/CD5+ cells and with the levels of all other apoptosis-modulating proteins tested. Binary logistic regression analysis demonstrated the ability to predict probability of disease with over 90% accuracy. Finally, based on the changes in the levels of several proteins in CLL patients, as revealed from LC-HR-MS/MS, we could distinguish between patients in a stable disease state and those who would be later transferred to anti-cancer treatments. The over-expressed proteins can thus serve as potential biomarkers for early diagnosis, prognosis, new targets for CLL therapy, and treatment guidance of CLL, forming the basis for personalized therapy.

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Urate: a novel biomarker of Parkinson's disease risk, diagnosis and prognosis.

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Urate: a novel biomarker of Parkinson's disease risk, diagnosis and prognosis.

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