Homocysteine and Parkinson's disease: A dangerous liaison?

Journal of the Neurological Sciences

Volumn 257, Issue 1-2, 2007, Pages 31-37

  Martignoni, E ^a,b   Tassorelli, C ^c   Nappi, G ^c,d   Zangaglia, R ^c   Pacchetti, C ^c   Blandini, F ^c  

^a IRCCS   (Italy)

^b UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^c C MONDINO NATIONAL NEUROLOGICAL INSTITUTE   (Italy)

^d SAPIENZA UNIVERSITY OF ROME   (Italy)

Author keywords

Cytotoxicity; Folic acid; l Dopa; Methylation; Movement disorders; Neurodegeneration; Vitamin B12

Indexed keywords

CYANOCOBALAMIN; FOLIC ACID; HOMOCYSTEINE; LEVODOPA; METHIONINE; PYRIDOXINE;

AMINO ACID BLOOD LEVEL; ARTICLE; BRAIN ATROPHY; CATABOLISM; CLINICAL FEATURE; CYTOTOXICITY; DEMETHYLATION; FOLIC ACID DEFICIENCY; GENE MUTATION; GENOTYPE; HUMAN; HYPERHOMOCYSTEINEMIA; MENTAL DEFICIENCY; METHYLATION; NEUROTOXICITY; PARKINSON DISEASE; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RISK FACTOR; SEIZURE; VITAMIN DEFICIENCY;

BRAIN; BRAIN DISEASES, METABOLIC; CAUSALITY; HOMOCYSTEINE; HUMANS; HYPERHOMOCYSTEINEMIA; LEVODOPA; NERVE DEGENERATION; PARKINSON DISEASE;

EID: 34249796691     PISSN: 0022510X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jns.2007.01.028     Document Type: Article

References (77)

1. Stead L.M., Jacobs R.L., Brosnan M.E., and Brosnan J.T. Methylation demand and homocysteine metabolism. Adv Enzyme Regul 44 (2004) 321-333
2. Mattson M.P., and Shea T.B. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26 (2003) 137-146
3. Selhub J. Homocysteine metabolism. Annu Rev Nutr 19 (1999) 217-246
4. Christensen B., Refsum H., Vintermyr O., and Ueland P.M. Homocysteine export from cells cultured in the presence of physiological or superfluous levels of methionine: methionine loading of non-transformed, transformed, proliferating, and quiescent cells in culture. J Cell Physiol 146 (1991) 52-62
5. Miller J.W., Nadeau M.R., Smith J., Smith D., and Selhub J. Folate-deficiency-induced homocysteinaemia in rats: disruption of S-adenosylmethionine's co-ordinate regulation of homocysteine metabolism. Biochem J 298 Pt 2 (1994) 415-419
6. van den B.M., van der Knaap M.S., Boers G.H., Stehouwer C.D., Rauwerda J.A., and Valk J. Hyperhomocysteinaemia; with reference to its neuroradiological aspects. Neuroradiology 37 (1995) 403-411
7. Watkins D., and Rosenblatt D.S. Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. Am J Med Genet 3 (1989) 427-434
8. Andreotti F., Burzotta F., Manzoli A., and Robinson K. Homocysteine and risk of cardiovascular disease. J Thromb Thrombolysis 9 (2000) 13-21
9. Perry I.J. Serum total homocysteine concentration and risk of stroke. Lancet 348 (1996) 1526
10. Temple M.E., Luzier A.B., and Kazierad D.J. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 34 (2000) 57-65
11. Blundell G., Rose F.A., and Tudball N. Homocysteine induced endothelial cell toxicity and its protection. Biochem Soc Trans 22 (1994) 341S
12. Blundell G., Jones B.G., Rose F.A., and Tudball N. Homocysteine mediated endothelial cell toxicity and its amelioration. Atherosclerosis 122 (1996) 163-172
13. Abdelfatah A., Ducloux D., Toubin G., Motte G., Alber D., and Chalopin J.M. Treatment of hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients. Transplantation 73 (2002) 663-665
14. Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest 98 (1996) 5-7
15. Mujumdar V.S., Aru G.M., and Tyagi S.C. Aru GM, Tyagi SC. Induction of oxidative stress by homocyst(e)ine impairs endothelial function. J Cell Biochem 82 (2001) 491-500
16. Suhara T., Fukuo K., Yasuda O., Tsubakimoto M., Takemura Y., Kawamoto H., et al. Homocysteine enhances endothelial apoptosis via upregulation of Fas-mediated pathways. Hypertension 43 (2004) 1208-1213
17. Bessede G., Miguet C., Gambert P., Neel D., and Lizard G. Efficiency of homocysteine plus copper in inducing apoptosis is inversely proportional to gamma-glutamyl transpeptidase activity. FASEB J 15 (2001) 1927-1940
18. Zhang C., Cai Y., Adachi M.T., Oshiro S., Aso T., Kaufman R.J., et al. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem 276 (2001) 35867-35874
19. Kruman I.I., Culmsee C., Chan S.L., Kruman Y., Guo Z., Penix L., et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 20 (2000) 6920-6926
20. Buttke T.M., and Sandstrom P.A. Oxidative stress as a mediator of apoptosis. Immunol Today 15 (1994) 7-10
21. Huerta J.M., Gonzalez S., Fernandez S., Patterson A.M., and Lasheras C. No evidence for oxidative stress as a mechanism of action of hyperhomocysteinemia in humans. Free Radic Res 38 (2004) 1215-1221
22. Mangiagalli A., Samuele A., Armentero M.T., Bazzini E., Nappi G., and Blandini F. Effects of homocysteine on apoptosis-related proteins and anti-oxidant systems in isolated human lymphocytes. Eur J Biochem 271 (2004) 1671-1676
23. Jacob R.A., Gretz D.M., Taylor P.C., James S.J., Pogribny I.P., Miller B.J., et al. Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr 128 (1998) 1204-1212
24. Siri P.W., Verhoef P., and Kok F.J. Vitamins B6, B12, and folate: association with plasma total homocysteine and risk of coronary atherosclerosis. J Am Coll Nutr 17 (1998) 435-441
25. Frosst P., Blom H.J., Milos R., Goyette P., Sheppard C.A., Matthews R.G., et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10 (1995) 111-113
26. Jhee K.H., and Kruger W.D. The role of cystathionine beta-synthase in homocysteine metabolism. Antioxid Redox Signal 7 (2005) 813-822
27. Deloughery T.G., Evans A., Sadeghi A., McWilliams J., Henner W.D., and Taylor Jr. L.M. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late-onset vascular disease. Circulation 94 (1996) 3074-3078
28. Ma J., Stampfer M.J., Hennekens C.H., Frosst P., Selhub J., Horsford J., et al. Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. Circulation 94 (1996) 2410-2416
29. Carmel R., Green R., Rosenblatt D.S., and Watkins D. Update on cobalamin, folate, and homocysteine. Hematology (Am Soc Hematol Educ Program) (2003) 62-81
30. Troen A.M. The central nervous system in animal models of hyperhomocysteinemia. Prog Neuropsychopharmacol Biol Psychiatry 29 (2005) 1140-1151
31. Pogribny I.P., Basnakian A.G., Miller B.J., Lopatina N.G., Poirier L.A., and James S.J. Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate/methyl-deficient rats. Cancer Res 55 (1995) 1894-18901
32. Wainfan E., and Poirier L.A. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res 52 (1992) 2071s-2077s
33. Herrmann W., and Knapp J.P. Hyperhomocysteinemia: a new risk factor for degenerative diseases. Clin Lab 48 (2002) 471-481
34. Schlussel E., Preibisch G., Putter S., and Elstner E.F. Homocysteine-induced oxidative damage: mechanisms and possible roles in neurodegenerative and atherogenic processes. Z Naturforsch [C] 50 (1995) 699-707
35. Thompson G.A., and Kilpatrick I.C. The neurotransmitter candidature of sulphur-containing excitatory amino acids in the mammalian central nervous system. Pharmacol Ther 72 (1996) 25-36
36. Ho P.I., Ortiz D., Rogers E., and Shea T.B. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage. J Neurosci Res 70 (2002) 694-702
37. Kruman I.I., Kumaravel T.S., Lohani A., Pedersen W.A., Cutler R.G., Kruman Y., et al. Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci 22 (2002) 1752-1762
38. Lipton S.A., Kim W.K., Choi Y.B., Kumar S., D'Emilia D.M., Rayudu P.V., et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-d-aspartate receptor. Proc Natl Acad Sci U S A 94 (1997) 5923-5928
39. Duan W., Ladenheim B., Cutler R.G., Kruman I.I., Cadet J.L., and Mattson M.P. Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. J Neurochem 80 (2002) 101-110
40. Benson R., Crowell B., Hill B., Doonquah K., and Charlton C. The effects of l-dopa on the activity of methionine adenosyltransferase: relevance to l-dopa therapy and tolerance. Neurochem Res 18 (1993) 325-330
41. Miller J.W., Shukitt-Hale B., Villalobos-Molina R., Nadeau M.R., Selhub J., and Joseph J.A. Effect of l-Dopa and the catechol-O-methyltransferase inhibitor Ro 41-0960 on sulfur amino acid metabolites in rats. Clin Neuropharmacol 20 (1997) 55-66
42. Liu X.X., Wilson K., and Charlton C.G. Effects of l-dopa treatment on methylation in mouse brain: implications for the side effects of l-dopa. Life Sci 66 (2000) 2277-2288
43. Miller J.W., Shukitt-Hale B., Villalobos-Molina R., Nadeau M.R., Selhub J., and Joseph J.A. Effect of l-Dopa and the catechol-O-methyltransferase inhibitor Ro 41-0960 on sulfur amino acid metabolites in rats. Clin Neuropharmacol 20 (1997) 55-66
44. Allain P., Le Bjouil A., Cordillet E., Le Quay L., Bagheri H., and Montastruc J.L. Sulfate and cysteine levels in the plasma of patients with Parkinson's disease. Neurotoxicology 16 (1995) 527-529
45. Kuhn W., Roebroek R., Blom H., van Oppenraaij D., Przuntek H., Kretschmer A., et al. Elevated plasma levels of homocysteine in Parkinson's disease. Eur Neurol 40 (1998) 225-227
46. Rogers J.D., Sanchez-Saffon A., Frol A.B., and Diaz-Arrastia R. Elevated plasma homocysteine levels in patients treated with levodopa: association with vascular disease. Arch Neurol 60 (2003) 59-64
47. O'suilleabhain P.E., Bottiglieri T., Dewey Jr. R.B., Sharma S., and Diaz-Arrastia R. Modest increase in plasma homocysteine follows levodopa initiation in Parkinson's disease. Mov Disord 19 (2004) 1403-1408
48. O'suilleabhain P.E., Sung V., Hernandez C., Lacritz L., Dewey Jr. R.B., Bottiglieri T., et al. Elevated plasma homocysteine level in patients with Parkinson disease: motor, affective, and cognitive associations. Arch Neurol 61 (2004) 865-868
49. Lamberti P., Zoccolella S., Armenise E., Lamberti S.V., Fraddosio A., de Mari M., et al. Hyperhomocysteinemia in l-dopa treated Parkinson's disease patients: effect of cobalamin and folate administration. Eur J Neurol 12 (2005) 365-368
50. Zoccolella S., Lamberti P., Armenise E., de Mari M., Lamberti S.V., Mastronardi R., et al. Plasma homocysteine levels in Parkinson's disease: role of antiparkinsonian medications. Parkinsonism Relat Disord 11 (2005) 131-133
51. Blandini F., Fancellu R., Martignoni E., Mangiagalli A., Pacchetti C., Samuele A., et al. Plasma homocysteine and l-dopa metabolism in patients with Parkinson disease. Clin Chem 47 (2001) 1102-1104
52. Muller T., Werne B., Fowler B., and Kuhn W. Nigral endothelial dysfunction, homocysteine, and Parkinson's disease. Lancet 354 (1999) 126-127
53. Muller T., Woitalla D., Hauptmann B., Fowler B., and Kuhn W. Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson's disease. Neurosci Lett 308 (2001) 54-56
54. Fux R., Kloor D., Hermes M., Rock T., Proksch B., Grenz A., et al. Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and on DNA methylation of lymphocytes in healthy male volunteers. Am J Physiol Renal Physiol 289 (2005) F786-F792
55. Lerner V., Miodownik C., Kaptsan A., Vishne T., Sela B.A., and Levine J. High serum homocysteine levels in young male schizophrenic and schizoaffective patients with tardive parkinsonism and/or tardive dyskinesia. J Clin Psychiatry 66 (2005) 1558-1563
56. Goff D.C., Bottiglieri T., Arning E., Shih V., Freudenreich O., Evins A.E., et al. Folate, homocysteine, and negative symptoms in schizophrenia. Am J Psychiatry 161 (2004) 1705-1708
57. O'Donnell C., and Stephens T. The significance of homocysteine levels in schizophrenia. Am J Psychiatry 162 (2005) 1387-1388
58. Goff D.C. Letter to the editor. Am J Psychiatry 162 (2005) 1388-1389
59. de Lau L.M., Koudstaal P.J., van Meurs J.B.J., Uitterlinden A.G., Hofman A., and Breteler M.M.B. Methylenetetrahydrofolate reductase C677T genotype and PD. Ann Neurol 57 (2005) 927-930
60. Widner B., Leblhuber F., Frick B., Laich A., Artner-Dworzak E., and Fuchs D. Moderate hyperhomocysteinaemia and immune activation in Parkinson's disease. J Neural Transm 109 (2002) 1445-1452
61. Sato Y., Iwamoto J., Kanoko T., and Satoh K. Homocysteine as a predictive factor for hip fracture in elderly women with Parkinson's disease. Am J Med 118 (2005) 1250-1255
62. Jackson S.H. The reaction of homocysteine with aldehyde: an explanation of the collagen defects in homocystinuria. Clin Chim Acta 45 (1973) 215-217
63. Irizarry M.C., Gurol M.E., Raju S., Diaz-Arrastia R., Locascio J.J., Tennis M., et al. Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease. Neurology 65 (2005) 1402-1408
64. Sai X., Kawamura Y., Kokame K., Yamaguchi H., Shiraishi H., Suzuki R., et al. Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein. J Biol Chem 277 (2002) 12915-12920
65. Scarpa S., Fuso A., D'Anselmi F., and Cavallaro R.A. Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease?. FEBS Lett 541 (2003) 145-148
66. Tucker K.L., Qiao N., Scott T., Rosenberg I., and Spiro III A. High homocysteine and low B vitamins predict cognitive decline in aging men; the Veterans Affairs Normative Aging Study. Am J Clin Nutr 82 (2005) 627-635
67. Kado D.M., Karlamangla A.S., Huang M.H., Troen A., Rowe J.W., Selhub J., et al. Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging. Am J Med 118 (2005) 161-167
68. Mooijaart S.P., Gussekloo J., Frolich M., Jolles J., Stott D.J., Westendorp R.G., et al. Homocysteine, vitamin B12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study. Am J Clin Nutr 82 (2005) 866-871
69. Muller U.J., Frick B., Winkler C., Fuchs D., Wenning G.K., Poewe W., et al. Homocysteine and serum markers if immune activation in primary dystonia. Mov Disord 20 (2005) 1663-1667
70. Hamed S.A., and Nabeshima T. The high atherosclerotic risk among epileptics: the atheroprotective role of multivitamins. J Pharmacol Sci 98 (2005) 340-353
71. Sener U., Zorlu Y., Karaguzel O., Ozdamar O., Coker I., and Topbas M. Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6. Seizure 15 (2006) 79-85
72. Stott D.J., MacIntosh G., Lowe G.D., Rumley A., McMahon A.D., Langhorne P., et al. Westendorp Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease. Am J Clin Nutr 82 (2005) 1320-1326
73. Pathansali R., Mangoni A.A., Creagh-Brown B., Lan Z.C., Ngow G.I., Yuan X.F., et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr 43 (2006) 127-137
74. Boxer A.L., Kramer J.H., Johnston K., Goldman J., Finley R., and Miller B.L. Executive dysfunction in hyperhomocystinemia responds to homocysteine-lowering treatment. Neurology 64 (2005) 1431-1434
75. Postuma R.B., and Lang A.E. Homocysteine and l-Dopa: should Parkinson disease patients receive preventive therapy?. Neurology 63 (2004) 886-891
76. Chen H., Zhang S.M., Schwarzschild M.A., Hernan M.A., Logrocino G., Willett W.C., et al. Folate intake and risk of Parkinson's disease. Am J Epidemiol 160 (2004) 368-375
77. Ellinson M., Thomas J., and Patterson A. A critical evaluation of the relationship between serum vitamin B, folate and total homocysteine with cognitive impairment in the elderly. J Hum Nutr Diet 17 (2004) 371-383