Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: Implications for neurodegenerative diseases

Journal of Neurochemistry

Volumn 88, Issue 6, 2004, Pages 1555-1569

  Mandel, Silvia ^a   Weinreb, Orly ^a   Amit, Tamar ^a   Youdim, Moussa B H ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

EGCG; Green tea; Neuroprotective drugs; Oxidative stress; Parkinson's disease; Protein kinase C

Indexed keywords

ANTIOXIDANT; CHELATING AGENT; COPPER; EPIGALLOCATECHIN GALLATE; FLAVONOID; HYDROGEN PEROXIDE; IRON; NEUROPROTECTIVE AGENT; POLYPHENOL; REACTIVE OXYGEN METABOLITE; TRANSITION ELEMENT;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BLUEBERRY; BRAIN ISCHEMIA; BRAIN PERFUSION; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DRUG MECHANISM; HUMAN; HUNTINGTON CHOREA; INFLAMMATION; MONOTHERAPY; MOUSE; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TEA;

LETHRINIDAE; VACCINIUM;

EID: 1642382889     PISSN: 00223042     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1471-4159.2003.02291.x     Document Type: Review

References (150)

1. Abd El Mohsen M. M., Kuhnle G., Rechner A. R., Schroeter H., Rose S., Jenner P. and Rice-Evans C. A. (2002) Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic. Biol. Med. 33, 1693-1702.
2. Ahmad N., Feyes D. K., Nieminen A. L., Agarwal R. and Mukhtar H. (1997) Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J. Natl Cancer Inst. 89, 1881-1886.
3. Alessandrini A., Namura S., Moskowitz M. A. and Bonventre J. V. (1999) MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proc. Natl Acad. Sci. USA 96, 12866-12869.
4. Anderson J. W., Diwadkar V. A. and Bridges S. R. (1998) Selective effects of different antioxidants on oxidation of lipoproteins from rats. Proc. Soc. Exp. Biol. Med. 218, 376-381.
5. Aviram M., Domfeld L., Kaplan M., Coleman R., Gaitini D., Nitecki S., Hofman A., Rosenblat M., Volkova N., Presser D., Attias J., Hayek T. and Fuhrman B. (2002) Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp. Clin. Res. 28, 49-62.
6. Bar-Am O., Yogev-Falach M., Amit T., Sagi Y. and Youdim M.B.H. (2004a) Regulation of protein kinase C by the MAO-B inhibitor anti-Parkinson drug rasagiline and its anti-Alzheimer cholinesterase inhibitor derivatives in vivo. J. Neurochem. (in press).
7. Bar-Am O., Amil T. and Youdim M.B.H. (2004b) Contrasting neuroprotective and neurotoxic activity of the respective major metabolities of anti-Parkinson drugs, rasagiline and selegiline. Neurosci. Lett. 355, 169-172.
8. Bastianetto S., Ramassamy C., Dore S., Christen Y., Poirier J. and Quirion R. (2000) The Ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by β-amyloid. Eur. J. Neurosci. 12, 1882-1890.
9. Battaini F. (2001) Protein kinase C isoforms as therapeutic targets in nervous system disease states. Pharmacol. Res. 44, 353-361.
10. Beal M. F. (2003) Bioenergetic approaches for neuroprotection in Parkinson's disease. Ann. Neurol. 53, S39-S47; discussion S47-38.
11. Ben-Shachar D., Eshel G., Finberg J. P. and Youdim M. B. (1991) The iron chelator desferrioxamine (Desferal) retards 6-hydroxydopamine-induced degeneration of nigrostriatal dopamine neurons. J. Neurochem. 56, 1441-1444.
12. Ben Shachar D., Kahana N., Kampel V., Warshawsky A. and Youdim M. B. H. (2004) Neuroprotection by a novel brain-permeable iron chelator, VK-28, against 6-hydroxydopamine lession in rats. Neuropharmacology 46, 254-263.
13. Benussi L., Govoni S., Gasparini L., Binetti G., Trabucchi M., Bianchetti A. and Racchi M. (1998) Specific role for protein kinase Cα in the constitutive and regulated secretion of amyloid precursor protein in human skin fibroblasts. Neurosci. Lett. 240, 97-101.
14. Berra E., Municio M. M., Sanz L., Frutos S., Diaz-Meco M. T. and Moscat J. (1997) Positioning atypical protein kinase C isoforms in the UV-induced apoptotic signaling cascade. Mol. Cel. Biol. 17, 4346-4354.
15. Blum D., Torch S., Lambeng N., Nissou M., Benabid A. L., Sadoul R. and Verna J. M. (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease. Prog. Neurobiol. 65, 135-172.
16. Blum-Degen D., Muller T., Kuhn W., Gerlach M., Przuntek H. and Riederer P. (1995) Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci. Lett. 202, 17-20.
17. Bravo L. (1998) Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr. Rev. 56, 317-333.
18. Bush A. I. (2003) The metallobiology of Alzheimer's disease. Trends Neurosci. 26, 207-214.
19. Busto R., Globus M. Y., Neary J. T. and Ginsberg M. D. (1994) Regional alterations of protein kinase C activity following transient cerebral ischemia: effects of intraischemic brain temperature modulation. J. Neurochem. 63, 1095-1103.
20. Cardell M. and Wieloch T. (1993) Time course of the translocation and inhibition of protein kinase C during complete cerebral ischemia in the rat. J. Neurochem. 61, 1308-1314.
21. Checkoway H., Powers K., Smith-Weller T., Franklin G. M., Longstreth W. T. Jr and Swanson P. D. (2002) Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am. J. Epidemiol. 155, 732-738.
22. Checler F. (1995) Processing of the β-amyloid precursor protein and its regulation in Alzheimer's disease. J. Neurochem. 65, 1431-1444.
23. Chen C., Yu R., Owuor E. D. and Kong A. N. (2000) Activation of antioxidant-response element (ARE), mitogen-activated protein kinases (MAPKs) and caspases by major green tea polyphenol components during cell survival and death. Arch. Pharm. Res. 23, 605-612.
24. Chemy R. A., Atwood C. S., Xilinas M. E. et al. (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30, 665-676.
25. Choi Y. T., Jung C. H., Lee S. R., Bae J. H., Baek W. K., Suh M. H., Park J., Park C. W. and Suh S. I. (2001) The green tea polyphenol (-)-epigallocatechin gallate attenuates β-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci. 70, 603-614.
26. Chow H. H., Cai Y., Alberts D. S., Hakim I., Dorr R., Shahi F., Crowell J. A., Yang C. S. and Hara Y. (2001) Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenol. E. Cancer Epidemiol. Biomarkers Prev. 10, 53-58.
27. Chung J. H., Han J. H., Hwang E. J., Seo J. Y., Cho K. H., Kim K. H., Youn J. I. and Eun H. C. (2003) Dual mechanisms of green tea extract-induced cell survival in human epidermal keratinocytes. Faseb J. 17, 1913-1915.
28. Cordey M., Gundimeda U., Gopalakrishna R. and Pike C. J. (2003) Estrogen activates protein kinase C in neurons: role in neuroprotection. J. Neurochem. 84, 1340-1348.
29. Deleu D., Northway M. G. and Hanssens Y. (2002) Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin. Pharmacokinet. 41, 261-309.
30. Dempsey E. C., Newton A. C., Mochly-Rosen D., Fields A. P., Reyland M. E., Insel P. A. and Messing R. O. (2000) Protein kinase C isozymes and the regulation of diverse cell responses. Am. J. Physiol. Lung Cell Mol. Physiol. 279, L429-L438.
31. Dufresne C. and Farnworth E. (2001) A review of latest research findings on the health promotion properties of tea. J. Nutr. Biochem. 12, 404-421.
32. Fuhrman B., Lavy A. and Aviram M. (1995) Consumption of red wine with meals reduces the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Am. J. Clin. Nutr. 61, 549-554.
33. Fuhrman B., Buch S., Vaya J., Belinky P. A., Coleman R., Hayek T. and Aviram M. (1997) Licorice extract and its major polyphenol glabridin protect low-density lipoprotein against lipid peroxidation: in vitro and ex vivo studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am. J. Clin. Nutr. 66, 267-275.
34. Gassen M. and Youdim M. B. (1997) The potential role of iron chelators in the treatment of Parkinson's disease and related neurological disorders. Pharmacol. Toxicol. 80, 159-166.
35. Gassen M. and Youdim M. B. H. (1999) Free radical scavengers: chemical concepts and clinical relevance. J. Neural Transm. Suppl. 56, 193-210.
36. Gassen M., Glinka Y., Pinchasi B. and Youdim M. B. H. (1996) Apomorphine is a highly potent free radical scavenger in rat brain mitochondrial fraction. Eur. J. Pharmacol. 308, 219-225.
37. Gassen M., Gross A. and Youdim M. B. (1998) Apomorphine enantiomers protect cultured pheochromocytoma (PC12) cells from oxidative stress induced by H2O2 and 6-hydroxydopamine. Mov. Disord. 13, 242-248.
38. Gerlach M., Double K. L., Ben-Shachar D., Zecca L., Youdim M. B. and Riederer P. (2003) Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease. Neurotox. Res. 5, 35-44.
39. Graham H. N. (1992) Green tea composition, consumption, and polyphenol chemistry. Prev. Med. 21, 334-350.
40. Gressens P., Marret S., Martin J. L., Laquerriere A., Lombet A. and Evrard P. (1998) Regulation of neuroprotective action of vasoactive intestinal peptide in the murine developing brain by protein kinase C and mitogen-activated protein kinase cascades: in vivo and in vitro studies. J. Neurochem. 70, 2574-2584.
41. Gressens P., Marret S., Bodenant C., Schwendimann L. and Evrard P. (1999) Activity-dependent neurotrophic factor-14 requires protein kinase C and mitogen-associated protein kinase kinase activation to protect the developing mouse brain against excitotoxicity. J. Mol. Neurosci. 13, 199-210.
42. Grinberg L. N., Newmark H., Kitrossky N., Rahamim E., Chevion M. and Rachmilewitz E. A. (1997) Protective effects of tea polyphenols against oxidative damage to red blood cells. Biochem. Pharmacol. 54, 973-978.
43. Grunblatt E., Mandel S., Berkuzki T. and Youdim M. B. H. (1999) Apomorphine protects against MPTP-induced neurotoxicity in mice. Mov. Disord. 14, 612-618.
44. Grunblatt E., Mandel S., Maor G. and Youdim M. B. H. (2001a) Gene expression analysis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease using cDNA microarray: effect of R-apomorphine. J. Neurochem. 78, 1-12.
45. Grunblatt E., Mandel S., Maor G. and youdim M. B. H. (2001b) Effects of R-apomorphine and S-apomorphine on MPTP-induced nigrostriatal doamine neuronal loss. J. Neurochem. 77, 146-156.
46. Gubina E., Rinaudo M. S., Szallasi Z., Blumberg P. M. and Mufson R. A. (1998) Overexpression of protein kinase C isoform ε but not Δ in human interleukin-3-dependent cells suppresses apoptosis and induces bcl-2 expression. Blood 91, 823-829.
47. Guo Q., Zhao B., Li M., Shen S. and Xin W. (1996) Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. Biochim. Biophys. Acta 1304, 210-222.
48. Halliwell B. (1996) Vitamin C: antioxidant or pro-oxidant in vivo? Free Radic. Res. 25, 439-454.
49. Haqqi T. M., Anthony D. D., Gupta S., Ahmad N., Lee M. S., Kumar G. K. and Mukhtar H. (1999) Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea. Proc. Natl Acad. Sci. USA 96, 4524-4529.
50. Harada M., Kan Y., Naoki H., Fukui Y., Kageyama N., Nakai M., Miki W. and Kiso Y. (1999) Identification of the major antioxidative metabolites in biological fluids of the rat with ingested (+)-catechin and (-)-epicatechin. Biosci. Biotechnol. Biochem. 63, 973-977.
51. Harris C. A., Deshmukh M., Tsui-Pierchala B., Maroney A. C. and Johnson E. M. Jr (2002) Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons. J. Neurosci. 22, 103-113.
52. Hastak K., Gupta S., Ahmad N., Agarwal M. K., Agarwal M. L. and Mukhtar H. (2003) Role of p53 and NF-κB in epigallocatechin-3-gallate-induced apoptosis of LNCaP cells. Oncogene 22, 4851-4859.
53. Higdon J. V. and Frei B. (2003) Tea catechins and polyphenols: health effects, metabolism, and andoxidant functions. Crit. Rev. Food Sci. Nutr. 43, 89-143.
54. Hunot S., Brugg B., Ricard D., Michel P. P., Muriel M. P., Ruberg M., Faucheux B. A., Agid Y. and Hirsch E. C. (1997) Nuclear translocation of NF-κB is increased in dopaminergic neurons of patients with parkinson disease. Proc. Natl Acad. Sci. USA 94, 7531-7536.
55. Ishige K., Schubert D. and Sagara Y. (2001) Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic. Biol. Med. 30, 433-446.
56. Jellinger K., Paulus W., Grundke-Iqbal I., Riederer P. and Youdim M. B. H. (1990) Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J. Neural Transm. Park. Dis. Dement. Sect. 2, 327-340.
57. Jenner P. and Olanow C. W. (1996) Oxidative stress and the pathogenesis of Parkinson's disease. Neurology 47, S161-S170.
58. Johnson G. L. and Lapadat R. (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912.
59. Joseph J. A., Shukitt-Hale B., Denisova N. A., Bielinski D., Martin A., McEwen J. J. and Bickford P. C. (1999) Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J. Neurosci. 19, 8114-8121.
60. Kaplan D. R. and Miller F. D. (2000) Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10, 381-391.
61. Kaur D., Yantiri F., Rajagopalan S. et al. (2003) Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron. 37, 899-909.
62. Kim S., Lee M. J., Hong J., Li C., Smith T. J., Yang G. Y., Seril D. N. and Yang C. S. (2000) Plasma and tissue levels of tea catechins in rats and mice during chronic consumption of green tea polyphenols. Nutr. Cancer 37, 41-48.
63. Kinouchi T., Ono Y., Sorimachi H., Ishiura S. and Suzuki K. (1995) Arachidonate metabolites affect the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein. Biochem. Biophys. Res. Commun. 209, 841-849.
64. Komatsu M. and Hiramatsu M. (2000) The efficacy of an antioxidant cocktail on lipid peroxide level and superoxide dismutase activity in aged rat brain and DNA damage in iron-induced epileptogenic foci. Toxicology 148, 143-148.
65. Kumamoto M., Sonda T., Nagayama K. and Tabata M. (2001) Effects of pH and metal ions on antioxidative activities of catechins. Biosci. Biotechnol. Biochem. 65, 126-132.
66. Kumari M. V., Yoneda T. and Hiramatsu M. (1997) Effect of 'beta CATECHIN' on the life span of senescence accelerated mice (SAM-P8 strain). Biochem. Mol. Biol. Int. 41, 1005-1011.
67. Lan J. and Jiang D. H. (1997) Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice. J. Neural Transm. 104, 469-481.
68. Lee S., Suh S. and Kim S. (2000) Protective effects of the green tea polyphenol (-)-epigallocatechin gallate against hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci. Lett. 287, 191-194.
69. Levites Y., Weinreb O., Maor G., Youdim M. B. H. and Mandel S. (2001) Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J. Neurochem. 78, 1073-1082.
70. Levites Y., Amit T., Youdim M. B. H. and Mandel S. (2002b) Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (-)-epigallocatechin-3-gallate neuroprotective action. J. Biol. Chem. 277, 30574-30580.
71. Levites Y., Youdim M. B. H., Maor G. and Mandel S. (2002a) Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-κB) activation and cell death by tea extracts in neuronal cultures. Biochem. Pharmacol. 63, 21-29.
72. Levites Y., Amit T., Mandel S. and Youdim M. B. H. (2003) Neuroprotection and neurorescue against amyloid beta toxicity and PKC-dependent release of non-amyloidogenic soluble precusor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. Faseb. J. 17, 952-954.
73. Lin J. K., Liang Y. C. and Lin-Shiau S. Y. (1999a) Cancer chemoprevention by tea polyphenols through mitotic signal transduction blockade. Biochem. Pharmacol. 58, 911-915.
74. Lin Y. L. and Lin J. K. (1997) (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by downregulating lipopolysaccharide-induced activity of transcription factor nuclear factor-κB. Mol. Pharmacol. 52, 465-472.
75. Lin Y. L., Tsai S. H., Lin-Shiau S. Y., Ho C. T. and Lin J. K. (1999b) Theaflavin-3,3′-digallate from black tea blocks the nitric oxide synthase by downregulating the activation of NF-κaB in macrophages. Eur. J. Pharmacol. 367, 379-388.
76. Linazasoro G. (2002) Neuroprotection in Parkinson's disease: love story or mission impossible? Exp. Rev. Neurotherapeut. 2, 403-416.
77. Lu H., Meng X. and Yang C. S. (2003) Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (-) -epigallocatechin gallate. Drug Metab. Dispos. 31, 572-579.
78. Luo Y., Smith J. V., Paramasivam V. et al. (2002) Inhibition of amyloid-beta aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761. Proc. Natl Acad. Sci. USA 99, 12197-12202.
79. McGeer P. L. and McGeer E. G. (1995) The inflammatory response system of brain: implications for therapy of Alzheimer's and other neurodegenerative diseases. Brain Res. Brain Res. Rev. 21, 195-218.
80. McNaught K. S., Belizaire R., Jenner P., Olanow C. W. and Isacson O. (2002) Selective loss of 20S proteasome α-subunits in the substantia nigra pars compacta in Parkinson's disease. Neurosci. Lett. 326, 155-158.
81. Maher P. (2001) How protein kinase C activation protects nerve cells from oxidative stress-induced cell death. J. Neurosci. 21, 2929-2938.
82. Mandel S., Grünblatt E., Royak-Levites Y., Maor G. and Youdim M. B. H. (2002) Molecular events in dopaminergic neurodegeneration and neuroprotection in MPTP model of Parkinson's disease employing cDNA microarray. In: Brain Disease, Therapeutic Strategies and Repair, Vol. 34 (Said A. C. M., ed.), pp. 291-298. Martin Dunitz, London, UK.
83. Mandel S., Grünblatt E., Riederer P., Gerlach M. and Youdim M. B. H. (2003a) Neuroprotective strategies in Parkinson's disease: sn update on progress. CNS Drugs 17, 729-762.
84. Mandel S., Weinreb O. and Youdim M. B. (2003b). Using cDNA microarray to assess Parkinson's disease models and the effects of neuroprotective drugs. Trends Pharmacol. Sci. 24, 184-191.
85. Mandel S., Reznichenko L., Amit T. and Youdim M. (2003c) Green tea polyphenol (-)-epigallocatechin-3-gallate protects rat PC12 Cells from apoptosis induced by serum withdrawal. Neurotoxocity Res. 5, 419-424.
86. Masuda M., Suzui M. and Weinstein I. B. (2001) Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin. Cancer Res. 7, 4220-4229.
87. + toxicity in substantia nigra: protection by desferrioxamine. Brain Res. 773, 76-81.
88. Matsuoka Y., Hasegawa H., Okuda S., Muraki T., Uruno T. and Kubota K. (1995) Ameliorative effects of tea catechins on active oxygen-related nerve cell injuries. J. Pharmacol. Exp. Ther. 274, 602-608.
89. 2+-independent protein kinase C changes in the brain of patients with Alzheimer's disease. J. Neurochem. 67, 317-323.
90. Mattson M. P., Cheng B., Culwell A. R., Esch F. S., Lieberburg I. and Rydel R. E. (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein. Neuron 10, 243-254.
91. Mattson M. P., Barger S. W., Furukawa K., Bruce A. J., Wyss-Coray T., Mark R. J. and Mucke L. (1997) Cellular signaling roles of TGFβ, TNFα and -β APP in brain injury responses and Alzheimer's disease. Brain Res. Rev. 23, 47-61.
92. Merry D. E. and Korsmeyer S. J. (1997) Bcl-2 gene family in the nervous system. Annu. Rev. Neurosci. 20, 245-267.
93. Mills J. and Reiner P. B. (1999) Regulation of amyloid precursor protein cleavage. J. Neurochem. 72, 443-460.
94. Miloso M., Bertelli A. A., Nicolini G. and Tredici G. (1999) Resveratrol-induced activation of the mitogen-activated protein kinases, ERK1 and ERK2, in human neuroblastoma SH-SY5Y cells. Neurosci. Lett. 264, 141-144.
95. Mizuno Y., Ohta S., Tanaka M., Takamiya S., Suzuki K., Sato T., Oya H., Ozawa T. and Kagawa Y. (1989) Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem. Biophys. Res. Commun. 163, 1450-1455.
96. Mochizuki H., Imai H., Endo K., Yokomizo K., Murata Y., Hattori N. and Mizuno Y. (1994) Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. Neurosci. Lett. 168, 251-253.
97. Mogi M., Harada M., Kondo T., Riederer P., Inagaki H., Minami M. and Nagatsu T. (1994) Interleukin-1β, interleukin-6, epidermal growth factor and transforming growth factor-α are elevated in the brain from parkinsonian patients. Neurosci. Lett. 180, 147-150.
98. Monteiro H. P. and Winterbourn C. C. (1989) 6-Hydroxydopamine releases iron from ferritin and promotes ferritin-dependent lipid peroxidation. Biochem. Pharmacol. 38, 4177-4182.
99. Morel I., Lescoat G., Cogrel P., Sergent O., Pasdeloup N., Brissot P., Cillard P. and Cillard J. (1999) Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem. Pharmacol. 45, 13-19.
100. Morimoto T., Ohsawa I., Takamura C., Ishiguro M. and Kohsaka S. (1998) Involvement of amyloid precursor protein in functional synapse formation in cultured hippocampal neurons. J. Neurosci. Res. 51, 185-195.
101. Nakagawa K. and Miyazawa T. (1997) Absorption and distribution of tea catechin, (-)-epigallocatechin-3-gallate, in the rat. J. Nutr. Sci. Vitaminol. 43, 679-684.
102. Nanjo F., Goto K., Seto R., Suzuki M., Sakai M. and Hara Y. (1996) Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical. Free Rad Biol. Med. 21, 895-902.
103. Nishino N., Kitamura N., Nakai T., Hashimoto T. and Tanaka C. (1989) Phorbol ester binding sites in human brain: characterization, regional distribution, age-correlation, and alterations in Parkinson's disease. J. Mol. Neurosci. 1, 19-26.
104. Nunan J. and Small D. H. (2000) Regulation of APP cleavage by α-, β- and γ-secretases. FEBS Lett. 483, 6-10.
105. Oestreicher E., Sengstock G. J., Riederer P., Olanow C. W., Dunn A. J. and Arendash G. W. (1994) Degeneration of nigrostriatal dopaminergic neurons increases iron within the substantia nigra: a histochemical and neurochemical study. Brain Res. 660, 8-18.
106. Olanow C. W. and Youdim M. B. (1996) Iron and neurodegeneration: prospects for neuroprotection. In: Neurodegeneration and Neuroprotection in Parkinson's Disease, (Olanow C. W., Jenner P. and Youdim M. B., eds), pp. 55-69, Academic Press, London.
107. Owuor E. D. and Kong A. N. (2002) Antioxidants and oxidants regulated signal transduction pathways. Biochem. Pharmacol. 64, 765-770.
108. Pan M. H., Lin-Shiau S. Y., Ho C. T., Lin J. H. and Lin J. K. (2000) Suppression of lypopolysaccharide-induced nuclear factor κB activity by theaflavin-3,3′-digallate from black tea and other polyphenols through downregulation of I-κB kinase activity in macrophages. Biochem. Pharmacol. 59, 357-367.
109. +-induced dopamine neuron injury. Life Sci. 72, 1073-1083.
110. Parkinson Study Group (2002) A controlled trial of rasagiline in early Parkinson's disease: the TEMPO Study. Arch. Neurol. 59, 1937-1943.
111. Perry G., Cash A. D. and Smith M. A. (2002) Alzheimer's disease and oxidative stress. J. Biomed. Biotechnol. 2, 120-123.
112. Pratico D. and Delanty N. (2000) Oxidative injury in diseases of the central nervous system: focus on Alzheimer's disease. Am. J. Med. 109, 577-585.
113. Ravina B. M., Gagan S. C., Hart R. G., Hovinga C. A., Murphy D. D. and Dawson Marler J. R. (2003) Neuroprotective agents for clinical trials in Parkinson's disease. A systematic assessment. Neurology 60, 1234-1240.
114. Riederer P., Sofic E., Rausch W. D., Schmidt B., Reynolds G. P., Jéllinger K. and Youdim M. B. H. (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J. Neurochem. 52, 515-520.
115. Ruvolo P. P., Deng X., Carr B. K. and May W. S. (1998) A functional role for mitochondrial protein kinase C α in Bcl2 phosphorylation and suppression of apoptosis. J. Biol. Chem. 273, 25436-25442.
116. Sagi Y., Weinstock M. and Youdim M. B. (2003) Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor. J. Neurochem. 86, 290-297.
117. Sakaguchi S., Furusawa S., Yokota K., Sasaki K., Takayanagi M. and Takayanagi Y. (1996) The enhancing effect of tumour necrosis factor-alpha on oxidative stress in endotoxemia. Pharmacol. Toxicol. 79, 259-265.
118. Salah N., Miller N. J., Paganga G., Tijburg L., Bolwell G. P. and Rice-Evans C. (1995) Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch. Biochem. Biophy. 322, 339-346.
119. Schreck R., Rieber P. and Baeuerle P. A. (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-κB transcription factor and HIV-1. EMBO J. 10, 2247-2258.
120. Schroeter H., Boyd C., Spencer J. P., Williams R. J., Cadenas E. and Rice-Evans C. (2002) MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide. Neurobiol. Aging 23, 861-880.
121. Schroeter H., Spencer J. P., Rice-Evans C. and Williams R. J. (2001) Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3. Biochem. J. 358, 547-557.
122. Schubert D. and Behl C. (1993) The expression of amyloid beta protein precursor protects nerve cells from β-amyloid and glutamate toxicity and alters their interaction with the extracellular matrix. Brai.N Res. 629, 275-282.
123. Selkoe D. J. and Schenk D. (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol. 43, 545-584.
124. Serafini M., Ghiselli A. and Ferro-Luzzi A. (1996) In vivo antioxidant effect of green and black tea in man. Eur. J. Clin. Nutr. 50, 28-32.
125. Singer C. A., Figueroa-Masot X. A., Batchelor R. H. and Dorsa D. M. (1999) The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J. Neurosci. 19, 2455-2463.
126. Slack B. E., Nitsch R. M., Livneh E., Kunz G. M. Jr, Breu J., Eldar H. and Wurtman R. J. (1993) Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase C alpha. J. Biol. Chem. 268, 210972-21101.
127. Slikker W., Youdim M. B., Palmer G. C., Hall E., Williams C. and Trembly B. (1999) The future of neuroprotection. Ann. NY Acad. Sci. 890, 529-533.
128. Small D. H., Nurcombe V., Reed G., Clarris H., Moir R. and Beyreuther K. and Masters C. L. (1994) A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J. Neurosci. 14, 2117-2127.
129. Small D. L., Monette R., Chakravarthy B., Durkin J., Barbe G., Mealing G., Morley P. and Buchan A. M. (1996) Mechanisms of 1S,3R-ACPD-induced neuroprotection in rat hippocampal slices subjected to oxygen and glucose deprivation. Neuropharmacology 35, 1037-1048.
130. Sofic E., Paulus W., Jellinger K., Riederer P. and Youdim M. B. H. (1991) Selective increase of iron in substantia nigra zona compacta of parkinsonian brains. J. Neurochem. 56, 978-982.
131. Sofic E., Lange K. W., Jellinger K. and Riederer P. (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci. Lett. 142, 128-130.
132. Spillantini M. G., Schmidt M. L., Lee V. M., Trojanowski J. Q., Jakes R. and Goedert M. (1997) α-Synuclein in Lewy bodies. Nature 388, 839-840.
133. Suganuma M., Okabe S., Oniyama M., Tada Y., Ito H. and Fujiki H. (1998) Wide distribution of [3H] (-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 19, 1771-1776.
134. Sweeney M. I., Kalt W., MacKinnon S. L., Ashby J. and Gottschall-Pass K. T. (2002) Feeding rats diets enriched in lowbush blueberries for 6 weeks decreases ischemia-induced brain damage. Nutr. Neurosci. 5, 427-431.
135. Temlett J. A., Landsberg J. P., Watt F. and Grime G. W. (1994) Increased iron in the substantia nigra compacta of the MPTP-lesioned hemiparkinsonian African green monkey: evidence from proton microprobe elemental microanalysis. J. Neurochem. 62, 134-146.
136. Vaudry D., Stork P. J., Lazarovici P. and Eiden L. E. (2002) Signaling pathways for PC12 cell differentiation: making the right connections. Science 296, 1648-1649.
137. Wang Z. Y., Huang M. T., Lou Y. R., Xie J. G., Reuhl K. R., Newmark H. L., Ho C. T., Yang C. S. and Conney A. H. (1994) Inhibitory effects of black tea, green tea, decaffeinated black tea, and decaffeinated green tea on ultraviolet B light-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene-initiated SKH-1 mice. Cancer Res. 54, 3428-3455.
138. Ward C. P., Redd K., Williams B. M., Caler J. R., Luo Y. and McCoy J. G. (2002) Ginkgo biloba extract: cognitive enhancer or antistress buffer. Pharmacol. Biochem. Behav. 72, 913-922.
139. Weinreb O., Mandel S. and Youdim M. B. H. (2003a) CDNA gene expression profile homology of antioxidants and their anti-apoptotic and proapoptotic activities in human neuroblastoma cells. Faseb J.
140. Weinreb O., Mandel S. and Youdim M. B. (2003b) Gene and protein expression profiles of anti- and proapoptotic actions of dopamine, R.-apomorphine, green tea polyphenol (-)-epigallocatechine-3-gallate, and melatonin. Ann. NY Acad. Sci. 993, 351-361; discussion 387-393.
141. Whelan R. D. and Parker P. J. (1998) Loss of protein kinase C function induces an apoptotic response. Oncogene 16, 1939-1944.
142. Xia Z., Dickens M., Raingeaud J., Davis R. J. and Greenberg M. E. (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326-1331.
143. Xu X., Yang D., Wyss-Coray T., Yan J., Gan L., Sun Y. and Mucke L. (1999) Wild-type but not Alzheimer-mutant amyloid precursor protein confers resistance against p53-mediated apoptosis. Proc. Natl Acad. Sci. USA 96, 7547-7552.
144. Yang C. S. and Wang Z. Y. (1993) Tea and cancer. J. Natl Cancer Inst 85, 1038-1049.
145. Yang F., de Villiers W. J., McClain C. J. and Varilek G. W. (1998) Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model. J. Nutr. 128, 2334-2340.
146. Yeon S. W., Jung M. W., Ha M. J., Kim S. U., Huh K., Savage M. J., Masliah E. and Mook-Jung I. (2001) Blockade of PKC epsilon activation attenuates phorbol ester-induced increase of α-secretase-derived secreted form of amyloid precursor protein. Biochem. Biophys. Res. Commun. 280, 782-787.
147. Yogev-Falach M., Amit T., Bar-Am, O. and Youdim M. B. H. (2003) The importance of propargylamine moiety in the anti-Parkinson drug rasagiline and its derivatives in MAPK-dependent amyloid precursor protein processing. Faseb J. 17, 2325-2327.
148. Youdim M. B. H. and Riederer P. (2003) Iron in normal and pathological brain. In: Encyclopedia of Neuroscience (Smith B. and Adelman G., eds). Elsevier, Amsterdam.
149. Youdim M. B. H., Wadia A., Tatton N. A. and Weinstock M. (2001) The anti-Parkinson drug rasagiline and its cholinesterase inhibitor derivatives exert neuroprotection unrelated to MAO inhibition in cell culture and in vivo. Ann. NY Acad. Sci. 939, 450-458.
150. Yun H. Y., Gonzalez-Zulueta M., Dawson V. L. and Dawson T. M. (1998) Nitric oxide mediates N-methyl-D-aspartate receptor-induced activation of p21ras. Proc. Natl Acad. Sci. USA 95, 5773-5778.