尿酸與神經變性疾病_West China Medical Journal

Authors：

 夏階強 , 曹蓓 ,  商慧芳

四川大學華西醫院神經內科（成都，610041）;

Corresponding?author：

商慧芳, Email: hfshang@yahoo.com

Keywords：

神經變性疾病; 尿酸; 帕金森病; 阿爾茨海默病; 肌萎縮側索硬化

DOI：

10.7507/1002-0179.20140240

Video：

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目前研究發現尿酸水平與一些神經變性疾病，如帕金森病（PD）、阿爾茨海默病（AD）及肌萎縮側索硬化（ALS）的發病呈負相關，較高的血及腦脊液尿酸水平可延緩PD、亨廷頓病、多系統萎縮的進展，而低尿酸水平是否促進ALS和AD病情進展還存在爭議。尿酸主要通過抗氧化應激作用發揮對神經元的保護作用。調節尿酸水平可能成為神經變性疾病治療的新策略。

Citation： 夏階強, 曹蓓, 商慧芳. 尿酸與神經變性疾病. West China Medical Journal, 2014, 29(4): 791-794. doi: 10.7507/1002-0179.20140240 Copy

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2.	Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer:a hypothesis[J]. Proc Natl Acad Sci USA, 1981, 78(11):6858-6862.
3.	Squadrito GL, Cueto R, Splenser AE, et al. Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid[J]. Arch Biochem Biophys, 2000, 376(2):333-337.
4.	Davies KJ, Sevanian A, Muakkassah-Kelly SF, et al. Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid[J]. Biochem J, 1986, 235(3):747-754.
5.	Chen H, Mosley TH, Alonso A, et al. Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) study[J]. Am J Epidemiol, 2009, 169(9):1064-1069.
6.	Weisskopf MG, O' Reilly E, Chen H, et al. Plasma urate and risk of Parkinson's disease[J]. Am J Epidemiol, 2007, 166(5):561-567.
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8.	Euser SM, Hofman A, Westendorp RG, et al. Serum uric acid and cognitive function and dementia[J]. Brain, 2009, 132(Pt 2):377-382.
9.	Irizarry MC, Raman R, Schwarzschild MA, et al. Plasma urate and progression of mild cognitive impairment[J]. Neurodegener Dis, 2009, 6(1-2):23-28.
10.	Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS:further evidence for oxidative stress?[J]. J Neurol Sci, 2009, 285(1-2):95-99.
11.	Ikeda K, Hirayama T, Takazawa T, et al. Relationships between disease progression and serum levels of lipid, urate, creatinine and ferritin in Japanese patients with amyotrophic lateral sclerosis:a cross-sectional study[J]. Intern Med, 2012, 51(12):1501-1508.
12.	Paganoni S, Zhang M, Quiroz Zarate A, et al. Uric acid levels predict survival in men with amyotrophic lateral sclerosis[J]. J Neurol, 2012, 259(9):1923-1928.
13.	Auinger P, Kieburtz KM, Dermott MP. The relationship between uric acid levels and Huntington's disease progression[J]. Mov Disord, 2010, 25(2):224-228.
14.	Lee JE, Song SK, Sohn YH, et al. Uric acid as a potential disease modifier in patients with multiple system atrophy[J]. Mov Disord, 2011, 26(8):1533-1536.
15.	Winquist A, Steenland KShankar A. Higher serum uric acid associated with decreased Parkinson's disease prevalence in a large community-based survey[J]. Mov Disord, 2010, 25(7):932-936.
16.	De Vera M, Rahman MM, Rankin J, et al. Gout and the risk of Parkinson's disease:a cohort study[J]. Arthritis Rheum, 2008, 59(11):1549-1554.
17.	Alonso A, Rodriguez LA, Logroscino G, et al. Gout and risk of Parkinson disease:a prospective study[J]. Neurology, 2007, 69(17):1696-1700.
18.	Gao X, Chen H, Choi HK, et al. Diet, urate, and Parkinson's disease risk in men[J]. Am J Epidemiol, 2008, 167(7):831-838.
19.	Jesas S, Perez I, Caceres-Redondo MT, et al. Low serum uric acid concentration in Parkinson's disease in southern Spain[J]. Eur J Neurol, 2013, 20(1):208-210.
20.	Zhang HN, Guo JF, He D, et al. Lower serum UA levels in Parkinson's disease patients in the Chinese population[J]. Neurosci Lett, 2012, 514(2):152-155.
21.	Sun CC, Luo FF, Wei L, et al. Association of serum uric acid levels with the progression of Parkinson's disease in Chinese patients[J]. Chin Med J (Engl), 2012, 125(4):583-587.
22.	Andreadou E, Nikolaou C, Gournaras F, et al. Serum uric acid levels in patients with Parkinson's disease:their relationship to treatment and disease duration[J]. Clin Neurol Neurosurg, 2009, 111(9):724-728.
23.	Ascherio A, LeWitt PA, Xu K, et al. Urate as a predictor of the rate of clinical decline in Parkinson disease[J]. Arch Neurol, 2009, 66(12):1460-1468.
24.	Annanmaki T, Pessala-Driver A, Hokkanen L, et al. Uric acid associates with cognition in Parkinson's disease[J]. Parkinsonism Relat Disord, 2008, 14(7):576-578.
25.	Annanmaki T, Pohja M, Parviainen T, et al. Uric acid and cognition in Parkinson's disease:a follow-up study[J]. Parkinsonism Relat Disord, 2011, 17(5):333-337.
26.	Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease:recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease[J]. Alzheimers Dement, 2011, 7(3):280-292.
27.	Kim TS, Pae CU, Yoon SJ, et al. Decreased plasma antioxidants in patients with Alzheimer's disease[J]. Int J Geriatr Psychiatry, 2006, 21(4):344-348.
28.	Bowman GL, Shannon J, Frei B, et al. Uric acid as a CNS antioxidant[J]. J Alzheimers Dis, 2010, 19(4):1331-1336.
29.	Schretlen DJ, Inscore AB, Jinnah HA, et al. Serum uric acid and cognitive function in community-dwelling older adults[J]. Neuropsychology, 2007, 21(1):136-140.
30.	Ruggiero C, Cherubini A, Lauretani F, et al. Uric acid and dementia in community-dwelling older persons[J]. Dement Geriatr Cogn Disord, 2009, 27(4):382-389.
31.	Ikeda K, Kawabe KIwasaki Y. Do serum uric acid levels reflect oxidative stress in the progression of ALS?[J]. J Neurol Sci, 2009, 287(1-2):294.
32.	Zoccolella S, Simone IL, Capozzo R, et al. An exploratory study of serum urate levels in patients with amyotrophic lateral sclerosis[J]. J Neurol, 2011, 258(2):238-243.
33.	Beal MF, Matson WR, Storey E, et al. Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex[J]. J Neurol Sci, 1992, 108(1):80-87.
34.	Kim HJ, Jeon BSLee JY. Serum urate levels are not associated with survival in multiple system atrophy[J]. Parkinsonism Relat Disord, 2011, 17(5):400-401.
35.	Zhu TG, Wang XX, Luo WF, et al. Protective effects of urate against 6-OHDA-induced cell injury in PC12 cells through antioxidant action[J]. Neurosci Lett, 2012, 506(2):175-179.
36.	Guerreiro S, Ponceau A, Toulorge D, et al. Protection of midbrain dopaminergic neurons by the end-product of purine metabolism uric acid:potentiation by low-level depolarization[J]. J Neurochem, 2009, 109(4):1118-1128.
37.	Cipriani S, Desjardins CA, Burdett TC, et al. Urate and its transgenic depletion modulate neuronal vulnerability in a cellular model of Parkinson's disease[J]. PLoS One, 2012, 7(5):e37331.
38.	Scott GS, Cuzzocrea S, Genovese T, et al. Uric acid protects against secondary damage after spinal cord injury[J]. Proc Natl Acad Sci USA, 2005, 102(9):3483-3488.
39.	Hooper DC, Scott GS, Zborek A, et al. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis[J]. FASEB J, 2000, 14(5):691-698.
40.	Church WHWard VL. Uric acid is reduced in the substantia nigra in Parkinson's disease:effect on dopamine oxidation[J]. Brain Res Bull, 1994, 33(4):419-425.
41.	Gong L, Zhang QL, Zhang N, et al. Neuroprotection by urate on 6-OHDA-lesioned rat model of Parkinson's disease:linking to Akt/GSK3beta signaling pathway[J]. J Neurochem, 2012, 123(5):876-885.
42.	Du Y, Chen CP, Tseng CY, et al. Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity[J]. Glia, 2007, 55(5):463-472.

1. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases[J]. Nature, 2006, 443(7113):787-795.
2. Ames BN, Cathcart R, Schwiers E, et al. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer:a hypothesis[J]. Proc Natl Acad Sci USA, 1981, 78(11):6858-6862.
3. Squadrito GL, Cueto R, Splenser AE, et al. Reaction of uric acid with peroxynitrite and implications for the mechanism of neuroprotection by uric acid[J]. Arch Biochem Biophys, 2000, 376(2):333-337.
4. Davies KJ, Sevanian A, Muakkassah-Kelly SF, et al. Uric acid-iron ion complexes. A new aspect of the antioxidant functions of uric acid[J]. Biochem J, 1986, 235(3):747-754.
5. Chen H, Mosley TH, Alonso A, et al. Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) study[J]. Am J Epidemiol, 2009, 169(9):1064-1069.
6. Weisskopf MG, O' Reilly E, Chen H, et al. Plasma urate and risk of Parkinson's disease[J]. Am J Epidemiol, 2007, 166(5):561-567.
7. Schwarzschild MA, Schwid SR, Marek K, et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease[J]. Arch Neurol, 2008, 65(6):716-723.
8. Euser SM, Hofman A, Westendorp RG, et al. Serum uric acid and cognitive function and dementia[J]. Brain, 2009, 132(Pt 2):377-382.
9. Irizarry MC, Raman R, Schwarzschild MA, et al. Plasma urate and progression of mild cognitive impairment[J]. Neurodegener Dis, 2009, 6(1-2):23-28.
10. Keizman D, Ish-Shalom M, Berliner S, et al. Low uric acid levels in serum of patients with ALS:further evidence for oxidative stress?[J]. J Neurol Sci, 2009, 285(1-2):95-99.
11. Ikeda K, Hirayama T, Takazawa T, et al. Relationships between disease progression and serum levels of lipid, urate, creatinine and ferritin in Japanese patients with amyotrophic lateral sclerosis:a cross-sectional study[J]. Intern Med, 2012, 51(12):1501-1508.
12. Paganoni S, Zhang M, Quiroz Zarate A, et al. Uric acid levels predict survival in men with amyotrophic lateral sclerosis[J]. J Neurol, 2012, 259(9):1923-1928.
13. Auinger P, Kieburtz KM, Dermott MP. The relationship between uric acid levels and Huntington's disease progression[J]. Mov Disord, 2010, 25(2):224-228.
14. Lee JE, Song SK, Sohn YH, et al. Uric acid as a potential disease modifier in patients with multiple system atrophy[J]. Mov Disord, 2011, 26(8):1533-1536.
15. Winquist A, Steenland KShankar A. Higher serum uric acid associated with decreased Parkinson's disease prevalence in a large community-based survey[J]. Mov Disord, 2010, 25(7):932-936.
16. De Vera M, Rahman MM, Rankin J, et al. Gout and the risk of Parkinson's disease:a cohort study[J]. Arthritis Rheum, 2008, 59(11):1549-1554.
17. Alonso A, Rodriguez LA, Logroscino G, et al. Gout and risk of Parkinson disease:a prospective study[J]. Neurology, 2007, 69(17):1696-1700.
18. Gao X, Chen H, Choi HK, et al. Diet, urate, and Parkinson's disease risk in men[J]. Am J Epidemiol, 2008, 167(7):831-838.
19. Jesas S, Perez I, Caceres-Redondo MT, et al. Low serum uric acid concentration in Parkinson's disease in southern Spain[J]. Eur J Neurol, 2013, 20(1):208-210.
20. Zhang HN, Guo JF, He D, et al. Lower serum UA levels in Parkinson's disease patients in the Chinese population[J]. Neurosci Lett, 2012, 514(2):152-155.
21. Sun CC, Luo FF, Wei L, et al. Association of serum uric acid levels with the progression of Parkinson's disease in Chinese patients[J]. Chin Med J (Engl), 2012, 125(4):583-587.
22. Andreadou E, Nikolaou C, Gournaras F, et al. Serum uric acid levels in patients with Parkinson's disease:their relationship to treatment and disease duration[J]. Clin Neurol Neurosurg, 2009, 111(9):724-728.
23. Ascherio A, LeWitt PA, Xu K, et al. Urate as a predictor of the rate of clinical decline in Parkinson disease[J]. Arch Neurol, 2009, 66(12):1460-1468.
24. Annanmaki T, Pessala-Driver A, Hokkanen L, et al. Uric acid associates with cognition in Parkinson's disease[J]. Parkinsonism Relat Disord, 2008, 14(7):576-578.
25. Annanmaki T, Pohja M, Parviainen T, et al. Uric acid and cognition in Parkinson's disease:a follow-up study[J]. Parkinsonism Relat Disord, 2011, 17(5):333-337.
26. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer's disease:recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease[J]. Alzheimers Dement, 2011, 7(3):280-292.
27. Kim TS, Pae CU, Yoon SJ, et al. Decreased plasma antioxidants in patients with Alzheimer's disease[J]. Int J Geriatr Psychiatry, 2006, 21(4):344-348.
28. Bowman GL, Shannon J, Frei B, et al. Uric acid as a CNS antioxidant[J]. J Alzheimers Dis, 2010, 19(4):1331-1336.
29. Schretlen DJ, Inscore AB, Jinnah HA, et al. Serum uric acid and cognitive function in community-dwelling older adults[J]. Neuropsychology, 2007, 21(1):136-140.
30. Ruggiero C, Cherubini A, Lauretani F, et al. Uric acid and dementia in community-dwelling older persons[J]. Dement Geriatr Cogn Disord, 2009, 27(4):382-389.
31. Ikeda K, Kawabe KIwasaki Y. Do serum uric acid levels reflect oxidative stress in the progression of ALS?[J]. J Neurol Sci, 2009, 287(1-2):294.
32. Zoccolella S, Simone IL, Capozzo R, et al. An exploratory study of serum urate levels in patients with amyotrophic lateral sclerosis[J]. J Neurol, 2011, 258(2):238-243.
33. Beal MF, Matson WR, Storey E, et al. Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex[J]. J Neurol Sci, 1992, 108(1):80-87.
34. Kim HJ, Jeon BSLee JY. Serum urate levels are not associated with survival in multiple system atrophy[J]. Parkinsonism Relat Disord, 2011, 17(5):400-401.
35. Zhu TG, Wang XX, Luo WF, et al. Protective effects of urate against 6-OHDA-induced cell injury in PC12 cells through antioxidant action[J]. Neurosci Lett, 2012, 506(2):175-179.
36. Guerreiro S, Ponceau A, Toulorge D, et al. Protection of midbrain dopaminergic neurons by the end-product of purine metabolism uric acid:potentiation by low-level depolarization[J]. J Neurochem, 2009, 109(4):1118-1128.
37. Cipriani S, Desjardins CA, Burdett TC, et al. Urate and its transgenic depletion modulate neuronal vulnerability in a cellular model of Parkinson's disease[J]. PLoS One, 2012, 7(5):e37331.
38. Scott GS, Cuzzocrea S, Genovese T, et al. Uric acid protects against secondary damage after spinal cord injury[J]. Proc Natl Acad Sci USA, 2005, 102(9):3483-3488.
39. Hooper DC, Scott GS, Zborek A, et al. Uric acid, a peroxynitrite scavenger, inhibits CNS inflammation, blood-CNS barrier permeability changes, and tissue damage in a mouse model of multiple sclerosis[J]. FASEB J, 2000, 14(5):691-698.
40. Church WHWard VL. Uric acid is reduced in the substantia nigra in Parkinson's disease:effect on dopamine oxidation[J]. Brain Res Bull, 1994, 33(4):419-425.
41. Gong L, Zhang QL, Zhang N, et al. Neuroprotection by urate on 6-OHDA-lesioned rat model of Parkinson's disease:linking to Akt/GSK3beta signaling pathway[J]. J Neurochem, 2012, 123(5):876-885.
42. Du Y, Chen CP, Tseng CY, et al. Astroglia-mediated effects of uric acid to protect spinal cord neurons from glutamate toxicity[J]. Glia, 2007, 55(5):463-472.

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