Article

Uric acid as a CNS antioxidant.

Department of Neurology, Layton Center for Aging and Alzheimer's Disease Research, Oregon Health & Science University, Portland, OR 97239, USA.
Journal of Alzheimer's disease: JAD (Impact Factor: 3.61). 01/2010; 19(4):1331-6. DOI: 10.3233/JAD-2010-1330
Source: PubMed

ABSTRACT Oxidative damage is a consistent finding in a number of central nervous system (CNS) disorders. Uric acid (UA) is a potent hydrophilic antioxidant that is modified by diet and drug. Several lines of evidence suggest that plasma UA may modulate outcomes in neurologic disease, but little attention has been paid to CNS levels of UA. Our objective was to test the hypothesis that cerebrospinal fluid (CSF) UA is determined by plasma UA, modified by blood-brain barrier (BBB) integrity and associated with rate of cognitive decline in Alzheimer's disease (AD). Also, since UA and ascorbic acid may act as antioxidants for one another, we also explored a potential interaction between them in the brain. Thirty-two patients with mild to moderate AD (Mini-Mental Status Exam 19 +/- 5) participated in a longitudinal biomarker study for one year involving standardized clinical assessments. CSF and blood were collected at baseline for UA, ascorbic acid, and albumin. Cognitive measures were collected at baseline and again one year later. CSF UA was independent of age, gender, and AD severity. CSF and plasma UA were positively correlated (r=0.669, p=0.001) and BBB impairment was associated with higher CSF levels of UA (p=0.028). Neither plasma nor CSF UA reached significant association with rates of cognitive decline over 1 year. CSF UA and CSF ascorbic acid were positively correlated (r=0.388, p=0.001). The hypothesis that CSF UA is determined by plasma UA and BBB integrity is supported, as is the hypothesis that UA and ascorbic acid are associated in CSF but not plasma. Adequately powered prospective studies would help assess any role for UA in primary and secondary prevention of AD.

0 Bookmarks
 · 
254 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this study was to investigate the association between gout and Parkinson's disease in older people in Taiwan. Utilizing the Taiwan National Health Insurance database, this case–control study included 3854 patients aged 65 years or older with newly diagnosed Parkinson's disease as the case group [mean age 75.0 years and standard deviation (SD) 5.0 years], and 15,416 patients without Parkinson's disease as the control group (mean age 74.0 years and SD 5.3 years). Multivariable logistic regression analysis detected no association between gout and Parkinson's disease in both sex [odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.86–1.12, in men and OR = 1.03, 95% CI = 0.88–1.21, in women, respectively]. We conclude that no association can be detected between gout and Parkinson's disease in older people in Taiwan.
    International Journal of Gerontology 09/2014; 8(3):166–167. · 0.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system - particularly the modulation of P1 and P2 receptor subtypes - plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 11/2014; PMID: 25445063. · 4.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Uric acid (UA) is an endogenous antioxidant which is known to reduce oxidative stress and also chelate iron ion. Recent studies have provided evidence that UA may play a neuroprotective role in Parkinson's disease (PD). However, it is unknown whether UA relates to nigral iron deposition, which is a characteristic pathophysiological alteration in PD. The aim of this study was to determine the potential relationship of these two markers in patients with PD.
    PLoS ONE 11/2014; 9(11):e112512. · 3.53 Impact Factor

Full-text

Download
100 Downloads
Available from
May 17, 2014