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.
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 .
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.
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.
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.
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.
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.
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.
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.
De Vera, M.; Rahman, M. M.; Rankin, J. Kopec, J.; Gao, X. and Choi, H. Abstract Arthritis Rheum. 59 (11):1549 - 1554.
Gout and the risk of Parkinson's disease: a cohort study.
Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Uric_acid.
This will list the latest papers on this topic. You are invited to update this page to reflect such recent results, pointing out their significance.
Use the following links to query the PubMed, PubMed Central and Google Scholar databases using the Search terms:- Parkinson's_Disease Urate.
- Substances with possible neuroprotective properties:
- Caffeine,--Celastrol,--Co-Enzyme Q10,--Creatine,--DHA,--Exendin-4 (EX-4),--GDNF,--Glutathione (GSH),--GM1,--Isradipine,--Melatonin,--Minocycline,--Nicotine,--NSAIDs,--Phenylbutyrate,--Phytic Acid,--Probucol,--Quinoxaline,--Rasagiline,--Riboflavin,--Statins,--Tolcapone,--Urate & Uric Acid,--Vitamin D,--Vitamin E,--
- Jones, D. C,; Gunasekar, P. G. ; Borowitz, J. L. and Isom, G. E. (2000) Abstract J. Meurochem. 74 (6) 2296-2304 Dopamine-induced apoptosis is mediated by oxidative stress and is enhanced by cyanide in differentiated PC12 cells .http://www.ncbi.nlm.nih.gov/pubmed/10820189
- Duan, W.; Ladenheim, B.; Cutler, R. G.; Kruman, I. I.; Cadet. J. L. and Mattson, M. P. (2002) Abstract J. Neurochem. 80 (1) 101 – 110 Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/11796748
- de Lau L. M. ; Koudstaal, P. J.; Hofman, A. and Breteler, M. M. (2006) Abstract Ann. Neurol. 58 (5) 797 – 800 Serum uric acid levels and the risk of Parkinson disease.http://www.ncbi.nlm.nih.gov/pubmed/16240356
- Alonso, A.; Rodríguez, L. A,; Logroscino, G. and Hernán, M. A.(2007) Abstract Neurology 69 17) 1696 – 1700. Gout and risk of Parkinson disease: a prospective study /http://www.ncbi.nlm.nih.gov/pubmed/17954784
- Davis, J. W.; Grandinetti, A.; Waslien, C. J.; Ross, G.W.; White, L.R. and Morens, D.M. (2007) Abstract Amer. J. of Epid. 144 (5) 480 - 484 Observations on Serum Uric Acid Levels and the Risk of Idiopathic Parkinson's Disease. http://aje.oxfordjournals.org/content/144/5/480.abstract
- Schwarzschild, M.A.; Schwid, S. R.; Marek, K.; Watts A.; Lang, A. E.; Oakes, D.; Shoulson, I.; Ascherio A.; Parkinson Study Group PRECEPT Investigators.; Hyson, C,; Gorbold, E.; Rudolph, A.; Kieburtz K,l. Fahn, S,; Gauger, L.; Goetz, C.; Seibyl, J.; Forrest, M and Ondrasik, J. (2008) Abstract Arch. Neurol. 65 (6) 716 – 723. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease http://www.ncbi.nlm.nih.gov/pubmed/18413464
- Chen, H.; Mosley, T. H.; alonso, A. and Huang, X. (2009) Abstract Am. Jnl. Epidemiol. 69 (9) 1064 - 1069, Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) study. http://www.ncbi.nlm.nih.gov/pubmed?term=chen%202009%20urate%20parkinson
- Ascherio, A.; LeWitt, P. A.; Xu, K.; Eberly, S.; Watts, A.; Matson, W. R.; Marras C.; Kieburtz K.; Rudolph, A..; Bogdanov, M. B.; Schwid, S. R.; Tennis, M.; Tanner, C. M.; Beal, M. F.; Lang, A. E.; Oakes D.; Fahn S.; Shoulson, I.; Schwarzschild, M. A. and Parkinson Study Group DATATOP Investigators. (2009) Abstract . Arch. Neurol. 66 (12) 1460-1468. Urate as a predictor of the rate of clinical decline in Parkinson disease. http://www.ncbi.nlm.nih.gov/pubmed/19822770
- Andreadou, E.; Nikolaou C.; Gournaras, F.; Rentzos, M.; Boufidou, F.’ Tsoutsou, A.; Zournas, C,; Zissimopoulos, V. and Vassilopoulos, D. (2009) Abstract Serum uric acid levels in patients with Parkinson's disease: their relationship to treatment and disease duration. http://www.ncbi.nlm.nih.gov/pubmed/19632030
- Alonso, A. and Sovell, K. (2010) Abstract Curr. Rheumatol. Rep.(2) 149 - 155. Gout, hyperuricemia, and Parkinson's disease: a protective effect? http://www.ncbi.nlm.nih.gov/pubmed/20425025
- Constantinescu, R. and Zetterberg, H (2011) Abstract Drugs Today (Barc). 47 (5):369 - 380. Urate as a marker of development and progression in Parkinson's disease. http://www.ncbi.nlm.nih.gov/pubmed/22013567