Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Urate & Uric Acid

"This page gives strong hints that urate levels in serum could serve as a biomarker for PD. Also that raising uric aid levels within safety limits would benefit PD patients."

Background
In humans Uric acid is metabolised in the kidneys and excreted in urine. It serves as an antioxidant. Over-expression of uric acid can lead to the formation of urate crystals, which accumulate in the lower extremities under the action of gravity and can give rise to the painful condition known as gout.

Research
2000

Jones et al treated dopaminergic cells with cyanide to mimic the Parkinsonian condition.

"These results suggest that DA neurotoxicity is enhanced under the conditions induced by cyanide and involves both ROS and nitric oxide-mediated oxidative stress as an initiator of apoptosis."

2002

Duan et al tested the hypothesis that dietary folate can modify vulnerability of dopaminergic neurons to dysfunction and death in a mouse model of PD. Their findings stated:-

"The adverse effects of homocysteine on dopaminergic cells is ameliorated by administration of the antioxidant uric acid and by an inhibitor of poly (ADP-ribose) polymerase. The ability of folate deficiency and elevated homocysteine levels to sensitize dopaminergic neurons to environmental toxins suggests a mechanism whereby dietary folate may influence risk for PD."

2005

de Lau et al carried out an epidemiological survey of 4,695 individuals over 9.4 years and found that higher serum levels of uric acid were associated with a significantly decreased risk of Parkinson disease. They concluded:-

"The findings suggest the hypothesis that oxidative stress contributes to the risk of Parkinson disease and suggest a potential protective effect of the natural antioxidant and free radical scavenger uric acid."

2007

Alonso et al carried out an epidemiological study of the association between gout diagnosis and the risk of PD. They used a General Practice Research Database with data on more than 3 million Britons and identified. PD cases occurring between January 1995 and December 2001. There was clear evidence that men with a history of gout carried a lower risk of getting PD.

Davis et al evaluated the health records of 7,938 men over a period of 30 years and found that those with an above average serum level of uric acid had a 40% less chance of contracting idiopathic PD.

2008

Schwarzschild et al tested the hypothesis that serum urate could be used as a predictor of clinical and radiographic progression for Parkinson’s disease. Their conclusions were:-

"These findings identify serum urate as the first molecular factor directly linked to thItalic texte progression of typical PD and suggest that targeting urate or its determinants could be an effective disease-modifying therapy in PD."

2009

Chen et al evaluated the risk association between gout and PD diagnoses. A cohort of 15,792 participants was recruited between 1987 to 1989 and followed annually since then. The inverse association of PD and plasma urate was confirmed.

Ascherio et al examined the relationship between blood urate and PD. They established a cohort of 800 subjects and made assessments. Their conclusions were:-

"Higher serum and cerebrospinal fluid urate concentrations at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate concentration and PD and the rationale for considering central nervous system urate concentration elevation as a potential strategy to slow PD progression."

Andreadou et al measured serum Uric acid levels in 43 PD patients and 47 healthy volunteers, age and sex-matched. UA levels were correlated with disease duration, severity and treatment. The results were:-

''There may be increased consumption of UA as a scavenger in PD, possibly heightened by dopaminergic drug treatment. Given the antioxidant properties of UA, manipulation of its concentrations should be investigated for potential therapeutic strategies of the disease.''

Alonso & Sovell reviewed the pathogenesis of PD.

''The risk of PD is also lower among individuals with gout. In addition, suggestive evidence from clinical studies shows high levels of uric acid as a marker of better prognosis in PD. Future research should determine the mechanisms underlying this association. This, in turn, could be used in the development of new preventive strategies and treatments for PD.''

2011

Constantinescu, R. and Zetterberg, H. reviewed the association of serum urate with the risk of PD, the clinical progression in PD, cognitive, dietary and gender aspects, the relationship between gout and PD, and potential therapeutic implications for the future.