In the rush for green gold: Can green tea delay age-progressive brain neurodegeneration?

Recent Patents on CNS Drug Discovery

Volumn 7, Issue 3, 2012, Pages 205-217

  Mandel, Silvia A ^a   Youdim, Moussa B H ^a,b  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b Yonsei University   (South Korea)

Author keywords

Alzheimer's disease; Combination therapy; Green tea polyphenols; Hypoxia inducible factor; Iron chelation; Neuroprotection neurorescue; Parkinson's disease

Indexed keywords

ALPHA TOCOPHEROL; ANTHOCYANIN; APIGENIN; ASCORBIC ACID; CATECHIN; EPICATECHIN; EPIGALLOCATECHIN GALLATE; FISETIN; FISH OIL; FLAVAN DERIVATIVE; FLAVANOL DERIVATIVE; FLAVONE DERIVATIVE; FLAVONOL DERIVATIVE; GALLOCATECHIN; GENISTEIN; GINKGO BILOBA EXTRACT; GLYCITEIN; GREEN TEA EXTRACT; HESPERETIN; ISOFLAVONE DERIVATIVE; KAEMPFEROL; LUTEOLIN; MYRICETIN; NARINGENIN; PELARGONIDIN; POLYPHENOL; PROANTHOCYANIDIN; QUERCETIN; THIOCTIC ACID; UNINDEXED DRUG;

AGING; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; BRAIN FUNCTION; COGNITION; COGNITIVE DEFECT; DEGENERATIVE DISEASE; DEMENTIA; DIET SUPPLEMENTATION; DIET THERAPY; DISEASE COURSE; HUMAN; HUNTINGTON CHOREA; KINESIOTHERAPY; LIFESTYLE MODIFICATION; MILD COGNITIVE IMPAIRMENT; NONHUMAN; NUTRITIONAL STATUS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; WINE;

AGING; ANIMALS; BRAIN; CATECHIN; DIETARY SUPPLEMENTS; FOOD HANDLING; HUMANS; NERVE TISSUE PROTEINS; NEURODEGENERATIVE DISEASES; NEURONS; NEUROPROTECTIVE AGENTS; OXIDATIVE STRESS; PATENTS AS TOPIC; TEA;

EID: 84867810508     PISSN: 15748898     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488912803252005     Document Type: Review

References (147)

1. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003; 39: 889-909.
2. Mandel S, Grunblatt E, Riederer P, Gerlach M, Levites Y, Youdim MBH. Neuroprotective Strategies in Parkinson's disease: An Update on Progress. CNS Drugs 2003;17: 729-62.
3. Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Jellinger K, et al. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 1989; 52: 515-20.
4. Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. Ann Neurol 1992; 32: 804-12.
5. Gerlach M, Ben-Shachar D, Riederer P, Youdim MB. Altered brain metabolism of iron as a cause of neurodegenerative diseases? J Neurochem 1994; 63:793-807.
6. Berg D, Gerlach M, Youdim MBH, Double KL, Zecca L, Riederer P, et al. Brain iron pathways and their relevance to Parkinson's disease. J Neurochem 2001; 79: 225-36.
7. Halliwell B. Reactive oxygen species and the central nervous system. J Neurochem 1992; 59: 1609-23.
8. Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010; 345: 91-104.
9. Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Sci 1992; 258: 1898-902.
10. Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009; 7:65-74.
11. Rossi L, Mazzitelli S, Arciello M, Capo CR, Rotilio G. Benefits from dietary polyphenols for brain aging and Alzheimer's disease. Neurochem Res 2008; 33: 2390-400.
12. Guglielmotto M, Giliberto L, Tamagno E, Tabaton M. Oxidative stress mediates the pathogenic effect of different Alzheimer's disease risk factors. Front Aging Neurosci 2010; 2:3-8.
13. Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, et al. Antioxidant approaches for the treatment of Alzheimer's disease. Expert Rev Neurother 2010; 10: 1201-8.
14. Cheng SY, Trombetta LD. The induction of amyloid precursor protein and alpha-synuclein in rat hippocampal astrocytes by diethyldithiocarbamate and copper with or without glutathione. Toxicol Lett 2004; 146: 139-49.
15. Patil S, Sheng L, Masserang A, Chan C. Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of Cterminal fragment of APP in primary cortical neurons. Neurosci Lett 2006; 406: 55-9.
16. Borghi R, Patriarca S, Traverso N, Piccini A, Storace D, Garuti A, et al. The increased activity of BACE1 correlates with oxidative stress in Alzheimer's disease. Neurobiol Aging 2007; 28: 1009-14.
17. Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, et al. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci U S A. 1994; 91: 3270-4.
18. Yatin SM, Varadarajan S, Link CD, Butterfield DA. In vitro and in vivo oxidative stress associated with Alzheimer's amyloid betapeptide (1-42). Neurobiol Aging 1999; 20: 325-30; discussion 39-42.
19. Duce JA, Bush AI. Biological metals and Alzheimer's disease: implications for therapeutics and diagnostics. Prog Neurobiol 2010; 92: 1-18.
20. Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, et al. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochem 1999; 38: 7609-16.
21. Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, et al. Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 1999; 274: 37111-6.
22. Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H, et al. An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript. J Biol Chem 2002; 277: 45518-28.
23. Silvestri L, Camaschella C. A potential pathogenetic role of iron in Alzheimer's disease. J Cell Mol Med 2008; 12: 1548-50.
24. Fahn S. Description of Parkinson's disease as a clinical syndrome. Ann N Y Acad Sci 2003; 991:1-14.
25. Jellinger KA. Recent developments in the pathology of Parkinson's disease. J Neural Transm Suppl 2002; 62: 347-76.
26. Sayre LM, Perry G, Harris PL, Liu Y, Schubert KA, Smith MA. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. J Neurochem 2000; 74: 270-9.
27. Vanhoutte G, Dewachter I, Borghgraef P, Van Leuven F, Van der Linden A. Noninvasive in vivo MRI detection of neuritic plaques associated with iron in APP[V717I] transgenic mice, a model for Alzheimer's disease. Magn Reson Med 2005; 53: 607-13.
28. Connor JR, Snyder BS, Beard JL, Fine RE, Mufson EJ. Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease. J Neurosci Res 1992; 31: 327-35.
29. Berg D. In vivo detection of iron and neuromelanin by transcranial sonography--a new approach for early detection of substantia nigra damage. J Neural Transm 2006; 113: 775-80.
30. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci 1998; 158: 47-52.
31. Pinero DJ, Hu J, Connor JR. Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's diseased brains. Cell Mol Biol (Noisy-Le-Grand). 2000; 46: 761-76.
32. Halliwell B. Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging. 2001; 18: 685-716.
33. Sayre LM, Smith MA, Perry G. Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr Med Chem 2001; 8: 721-38.
34. Friedlich AL, Tanzi RE, Rogers JT. The 5'-untranslated region of Parkinson's disease alpha-synuclein messengerRNA contains a predicted iron responsive element. Mol Psychiatry 2007; 12: 222-3.
35. Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci 2004; 5: 863-73.
36. Geldenhuys WJ, Youdim MB, Carroll RT, Van der Schyf CJ. The emergence of designed multiple ligands for neurodegenerative disorders. Prog Neurobiol 2011; 94: 347-59.
37. Amit T, Avramovich-Tirosh Y, Youdim MB, Mandel S. Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators. Faseb J. 2008; 22: 1296-305.
38. Mandel SA, Amit T, Weinreb O, Reznichenko L, Youdim MB. Simultaneous manipulation of multiple brain targets by green tea catechins: a potential neuroprotective strategy for Alzheimer and Parkinson diseases. CNS Neurosci Ther 2008; 14: 352-65.
39. Williams RJ, Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med 2012; 52: 35-45.
40. Abd El Mohsen MM, Kuhnle G, Rechner AR, Schroeter H, Rose S, Jenner P, et al. Uptake and metabolism of epicatechin and its access to the brain after oral ingestion. Free Radic Biol Med 2002; 33: 1693-702.
41. Lin LC, Wang MN, Tseng TY, Sung JS, Tsai TH. Pharmacokinetics of (-)-epigallocatechin-3-gallate in conscious and freely moving rats and its brain regional distribution. J Agric Food Chem 2007; 55: 1517-24.
42. Suganuma M, Okabe S, Oniyama M, Tada Y, Ito H, Fujiki H. Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis. 1998; 19: 1771-6.
43. Mandel SA, Amit T, Weinreb O, Youdim MB. Understanding the broad-spectrum neuroprotective action profile of green tea polyphenols in aging and neurodegenerative diseases. J Alzheimers Dis 2011; 25: 187-208.
44. Kennedy ET. Evidence for nutritional benefits in prolonging wellness. Am J Clin Nutr 2006; 83: 410S-4S.
45. Abbott A. Dementia: a problem for our age. Nature 2011; 475: S2-4.
46. National Institute on Aging & National Institutes of Health Report. Why population aging matters, a global perspective. 2007.
47. Farlow MR, Miller ML, Pejovic V. Treatment options in Alzheimer's disease: maximizing benefit, managing expectations. Dement Geriatr Cogn Disord 2008; 25: 408-22.
48. Luchsinger JA, Tang MX, Shea S, Mayeux R. Antioxidant vitamin intake and risk of Alzheimer disease. Arch Neurol 2003; 60: 203-8.
49. Morris MC, Beckett LA, Scherr PA, Hebert LE, Bennett DA, Field TS, et al. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 1998; 12: 121-6.
50. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alphatocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med 1997; 336: 1216-22.
51. Isaac MG, Quinn R, Tabet N. Vitamin E for Alzheimer's disease and mild cognitive impairment. Cochrane Database Syst Rev 2008; 16: CD002854.
52. Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev 2008; 8: CD004514.
53. Harrison FE. A Critical Review of Vitamin C for the Prevention of Age-Related Cognitive Decline and Alzheimer's Disease. J Alzheimers Dis 2012; 29: 711-26.
54. Storch A, Jost WH, Vieregge P, Spiegel J, Greulich W, Durner J, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q(10) in Parkinson disease. Arch Neurol 2007; 64: 938-44.
55. PSG. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group. N Engl J Med 1993; 328: 176-83.
56. Snitz BE, O'Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, et al. Ginkgo biloba for preventing cognitive decline in older adults: a randomized trial. Jama 2009; 302: 2663-70.
57. Freund-Levi Y, Hjorth E, Lindberg C, Cederholm T, Faxen-Irving G, Vedin I, et al. Effects of omega-3 fatty acids on inflammatory markers in cerebrospinal fluid and plasma in Alzheimer's disease: the OmegAD study. Dement Geriatr Cogn Disord 2009; 27: 481-90.
58. Baum L, Lam CW, Cheung SK, Kwok T, Lui V, Tsoh J, et al. Sixmonth randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008; 28: 110-3.
59. Lindsay J, Laurin D, Verreault R, Hebert R, Helliwell B, Hill GB, et al. Risk factors for Alzheimer's disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol 2002; 156: 445-53.
60. Luchsinger JA, Tang MX, Siddiqui M, Shea S, Mayeux R. Alcohol intake and risk of dementia. J Am Geriatr Soc 2004; 52: 540-6.
61. Truelsen T, Thudium D, Gronbaek M. Amount and type of alcohol and risk of dementia: the Copenhagen City Heart Study. Neurol 2002; 59: 1313-9.
62. Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, et al. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurol 2012; 78: 241-9.
63. Chan A, Paskavitz J, Remington R, Rasmussen S, Shea TB. Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension. Am J Alzheimers Dis Other Demen 2008; 23: 571-85.
64. Remington R, Chan A, Paskavitz J, Shea TB. Efficacy of a vitamin/nutriceutical formulation for moderate-stage to later-stage Alzheimer's disease: a placebo-controlled pilot study. Am J Alzheimers Dis Other Demen 2009; 24: 27-33.
65. Cornelli U. Treatment of Alzheimer's disease with a cholinesterase inhibitor combined with antioxidants. Neurodegener Dis 2010; 7: 193-202.
66. Ravina BM, Fagan SC, Hart RG, Hovinga CA, Murphy DD, Dawson TM, et al. Neuroprotective agents for clinical trials in Parkinson's disease: a systematic assessment. Neurol 2003; 60: 1234-40.
67. Investigators NN-P. A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Neurol 2007; 68: 20-8.
68. PSG. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurol 2006; 66: 664-71.
69. Gordon PH, Cheung YK, Levin B, Andrews H, Doorish C, Macarthur RB, et al. A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS. Amyotroph Lateral Scler. 2008;9:212-22.
70. Wang ZY, Huang MT, Lou YR, Xie JG, Reuhl KR, Newmark HL, et al. 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 1994; 54: 3428-55.
71. Yang CS, Wang ZY. Tea and cancer. J Natl Cancer Inst 1993; 85: 1038-49.
72. Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004; 79: 727-47.
73. Khokhar S, Magnusdottir SG. Total phenol, catechin, and caffeine contents of teas commonly consumed in the United kingdom. J Agric Food Chem 2002; 50: 565-70.
74. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 1992; 21: 334-50.
75. Pannala AS, Rice-Evans CA, Halliwell B, Singh S. Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols. Biochem Biophys Res Commun 1997; 232: 164-8.
76. Guo Q, Zhao B, Li M, Shen S, Xin W. Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. Biochim Biophys Acta 1996; 1304: 210-22.
77. Nanjo F, Goto K, Seto R, Suzuki M, Sakai M, Hara Y. Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picrylhydrazyl radical. Free Radic Biol Med 1996; 21: 895-902.
78. Spencer JP. Food for thought: the role of dietary flavonoids in enhancing human memory, learning and neuro-cognitive performance. Proc Nutr Soc 2008; 67: 238-52.
79. Levites Y, Weinreb O, Maor G, Youdim MBH, Mandel S. Green tea polyphenol (-)-Epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem 2001; 78: 1073-82.
80. Skrzydlewska E, Augustyniak A, Michalak K, Farbiszewski R. Green tea supplementation in rats of different ages mitigates ethanol-induced changes in brain antioxidant abilities. Alcohol 2005; 37: 89-98.
81. Srividhya R, Jyothilakshmi V, Arulmathi K, Senthilkumaran V, Kalaiselvi P. Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate. Int J Dev Neurosci 2008; 26: 217-23.
82. Assuncao M, Santos-Marques MJ, Carvalho F, Andrade JP. Green tea averts age-dependent decline of hippocampal signaling systems related to antioxidant defenses and survival. Free Radic Biol Med 2010; 48: 831-8.
83. Lin SM, Wang SW, Ho SC, Tang YL. Protective effect of green tea (-)-epigallocatechin-3-gallate against the monoamine oxidase B enzyme activity increase in adult rat brains. Nutrit 2010; 26: 1195-200.
84. Kim JS, Kim JM, Jeon BS. Inhibition of inducible nitric oxide synthase expression and cell death by (-)-epigallocatechin-3-gallate, a green tea catechin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. J Clin Neurosci17: 1165-8.
85. Spencer JP. Flavonoids and brain health: multiple effects underpinned by common mechanisms. Genes Nutr 2009; 4: 243-50.
86. Levites Y, Amit T, Mandel S, Youdim MBH. 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. 2003; 17: 952-4.
87. Reznichenko L, Amit T, Zheng H, Avramovich-Tirosh Y, Youdim MB, Weinreb O, et al. Reduction of iron-regulated amyloid precursor protein and beta-amyloid peptide by (-)-epigallocatechin-3-gallate in cell cultures: implications for iron chelation in Alzheimer's disease. J Neurochem 2006; 97: 527-36.
88. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, et al. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 2005; 25: 8807-14.
89. Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M. Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease. J Neurochem 2003; 87: 172-81.
90. Ono K, Yamada M. Antioxidant compounds have potent antifibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. J Neurochem 2006; 97: 105-15.
91. Thomas R, Kim MH. Epigallocatechin gallate inhibits HIF-1alpha degradation in prostate cancer cells. Biochem Biophys Res Commun 2005; 334: 543-8.
92. Zhou YD, Kim YP, Li XC, Baerson SR, Agarwal AK, Hodges TW, et al. Hypoxia-inducible factor-1 activation by (-)-epicatechin gallate: potential adverse effects of cancer chemoprevention with high-dose green tea extracts. J Nat Prod 2004; 67: 2063-9.
93. Kumari MV, Yoneda T, Hiramatsu M. Effect of "beta CATECHIN" on the life span of senescence accelerated mice (SAM-P8 strain). Biochem Mol Biol Int 1997; 41: 1005-11.
94. Li Q, Zhao HF, Zhang ZF, Liu ZG, Pei XR, Wang JB, et al. Longterm green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1-42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus. Neurosci 2009; 163:741-9.
95. Li Q, Zhao HF, Zhang ZF, Liu ZG, Pei XR, Wang JB, et al. Longterm administration of green tea catechins prevents age-related spatial learning and memory decline in C57BL/6 J mice by regulating hippocampal cyclic amp-response element binding protein signaling cascade. Neurosci 2009; 159: 1208-15.
96. Assuncao M, Santos-Marques MJ, Carvalho F, Lukoyanov NV, Andrade JP. Chronic green tea consumption prevents age-related changes in rat hippocampal formation. Neurobiol Aging 2011; 32: 707-17.
97. He M, Zhao L, Wei MJ, Yao WF, Zhao HS, Chen FJ. Neuroprotective effects of (-)-epigallocatechin-3-gallate on aging mice induced by D-galactose. Biol Pharm Bull 2009; 32: 55-60.
98. Zhang L, Jie G, Zhang J, Zhao B. Significant longevity-extending effects of EGCG on Caenorhabditis elegans under stress. Free Radic Biol Med 2009; 46: 414-21.
99. Lee S, Suh S, Kim S. Protective effects of the green tea polyphenol (-)-epigallocatechin gallate against hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci Let 2000; 287: 191-4.
100. Sutherland BA, Shaw OM, Clarkson AN, Jackson DM, Sammut IA, Appleton I. Neuroprotective effects of (-)-epigallocatechin gallate after hypoxia-ischemia-induced brain damage: novel mechanisms of action. Faseb J 2005; 19: 258-60.
101. Aktas O, Prozorovski T, Smorodchenko A, Savaskan NE, Lauster R, Kloetzel PM, et al. Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis. J Immunol. 2004; 173: 5794-800.
102. Park JW, Hong JS, Lee KS, Kim HY, Lee JJ, Lee SR. Green tea polyphenol (-)-epigallocatechin gallate reduces matrix metalloproteinase-9 activity following transient focal cerebral ischemia. J Nutr Biochem 2009; 21: 1038-44.
103. Koh SH, Lee SM, Kim HY, Lee KY, Lee YJ, Kim HT, et al. The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett 2006; 395: 103-7.
104. Chaturvedi RK, Shukla S, Seth K, Chauhan S, Sinha C, Shukla Y, et al. Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson's disease. Neurobiol Dis 2006; 22: 421-34.
105. Reznichenko L, Kalfon L, Amit T, Youdim MB, Mandel SA. Low dosage of Rasagiline and epigallocatechin gallate synergistically restored the nigrostriatal axis in MPTP-induced parkinsonism. Neurodegener Dis 2010; 7: 219-31.
106. Haque AM, Hashimoto M, Katakura M, Tanabe Y, Hara Y, Shido O. Long-term administration of green tea catechins improves spatial cognition learning ability in rats. J Nutr 2006; 136: 1043-7.
107. Haque AM, Hashimoto M, Katakura M, Hara Y, Shido O. Green tea catechins prevent cognitive deficits caused by Abeta(1-40) in rats. J Nutr Biochem 2008; 19: 619-26.
108. Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, et al. Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J Nutr 2009; 139: 1987-93.
109. Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res 2008; 1214: 177-87.
110. Obregon DF, Rezai-Zadeh K, Bai Y, Sun N, Hou H, Ehrhart J, et al. ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein. J Biol Chem 2006; 281: 16419-27.
111. Mandel SA, Avramovich-Tirosh Y, Reznichenko L, Zheng H, Weinreb O, Amit T, et al. Multifunctional activities of green tea catechins in neuroprotection. Neurosignals 2005; 14: 46-60.
112. Mattson MP, Barger SW, Furukawa K, Bruce AJ, Wyss-Coray T, Mark RJ, et al. Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer's disease. Brain Res Rev 1997; 23: 47-61.
113. Small DH, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K, et al. A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci 1994; 14: 2117-27.
114. Morimoto T, Ohsawa I, Takamura C, Ishiguro M, Kohsaka S. Involvement of amyloid precursor protein in functional synapse formation in cultured hippocampal neurons. J Neurosci Res 1998; 51: 185-95.
115. Shimmyo Y, Kihara T, Akaike A, Niidome T, Sugimoto H. Epigallocatechin-3-gallate and curcumin suppress amyloid betainduced beta-site APP cleaving enzyme-1 upregulation. Neuroreport 2008; 19: 1329-33.
116. Ehrnhoefer DE, Bieschke J, Boeddrich A, Herbst M, Masino L, Lurz R, et al. EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers. Nat Struct Mol Biol 2008; 15: 558-66.
117. Lee YK, Yuk DY, Lee JW, Lee SY, Ha TY, Oh KW, et al. (-)-Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency. Brain Res 2009; 1250: 164-74.
118. Giunta B, Obregon D, Hou H, Zeng J, Sun N, Nikolic V, et al. EGCG mitigates neurotoxicity mediated by HIV-1 proteins gp120 and Tat in the presence of IFN-gamma: role of JAK/STAT1 signaling and implications for HIV-associated dementia. Brain Res 2006; 1123: 216-25.
119. Ehrnhoefer DE, Duennwald M, Markovic P, Wacker JL, Engemann S, Roark M, et al. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum Mol Genet 2006; 15:2743-51.
120. Kumar P, Kumar A. Protective effects of epigallocatechin gallate following 3-nitropropionic acid-induced brain damage: possible nitric oxide mechanisms. Psychopharmacol (Berl). 2009; 207: 257-70.
121. PSG. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 2004; 61: 561-6.
122. Olanow CW, Rascol O, Hauser R, Feigin PD, Jankovic J, Lang A, et al. A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N Engl J Med 2009; 361: 1268-78.
123. Sagi Y, Mandel S, Amit T, Youdim MB. Activation of tyrosine kinase receptor signaling pathway by rasagiline facilitates neurorescue and restoration of nigrostriatal dopamine neurons in post-MPTP-induced parkinsonism. Neurobiol Dis 2007; 25: 35-44.
124. Zhu W, Xie W, Pan T, Jankovic J, Li J, Youdim MB, et al. Comparison of neuroprotective and neurorestorative capabilities of rasagiline and selegiline against lactacystin-induced nigrostriatal dopaminergic degeneration. J Neurochem 2008; 105: 1970-8.
125. Kuriyama S, Hozawa A, Ohmori K, Shimazu T, Matsui T, Ebihara S, et al. Green tea consumption and cognitive function: a crosssectional study from the Tsurugaya Project 1. Am J Clin Nutr 2006; 83: 355-61.
126. Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT, Jr., Swanson PD. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002; 155: 732-8.
127. Hu G, Bidel S, Jousilahti P, Antikainen R, Tuomilehto J. Coffee and tea consumption and the risk of Parkinson's disease. Mov Disord 2007; 22: 2242-8.
128. Tan LC, Koh WP, Yuan JM, Wang R, Au WL, Tan JH, et al. Differential effects of black versus green tea on risk of Parkinson's disease in the Singapore Chinese Health Study. Am J Epidemiol 2008; 167: 553-60.
129. Kandinov B, Giladi N, Korczyn AD. Smoking and tea consumption delay onset of Parkinson's disease. Parkinsonism Relat Disord 2009;15:41-6.
130. Hauser RA, Lew MF, Hurtig HI, Ondo WG, Wojcieszek J, Fitzer-Attas CJ. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease. Mov Disord 2009; 24: 564-73.
131. Chen CM, Lin JK, Liu SH, Lin-Shiau SY. Novel regimen through combination of memantine and tea polyphenol for neuroprotection against brain excitotoxicity. J Neurosci Res 2008; 86: 2696-704.
132. Giunta B, Hou H, Zhu Y, Salemi J, Ruscin A, Shytle RD, et al. Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice. Neurosci Lett 2010; 471: 134-8.
133. Ma QL, Yang F, Rosario ER, Ubeda OJ, Beech W, Gant DJ, et al. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J Neurosci 2009; 29: 9078-89.
134. Acosta S, Jernberg J, Sanberg CD, Sanberg PR, Small BJ, Gemma C, et al. NT-020, a Natural Therapeutic Approach to Optimize Spatial Memory Performance and Increase Neural Progenitor Cell Proliferation and Decrease Inflammation in the Aged Rat. Rejuvenation Res 2010; 13: 581-8.
135. Herges K, Millward JM, Hentschel N, Infante-Duarte C, Aktas O, Zipp F. Neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechin-3-gallate in neuroinflammation. PLoS One 2011; 6: e25456.
136. Ng TP, Feng L, Niti M, Kua EH, Yap KB. Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr 2008; 88: 224-31.
137. Huang CQ, Dong BR, Zhang YL, Wu HM, Liu QX. Association of cognitive impairment with smoking, alcohol consumption, tea consumption, and exercise among Chinese nonagenarians/centenarians. Cogn Behav Neurol 2009; 22: 190-6.
138. Olanow CW, Hauser RA, Jankovic J, Langston W, Lang A, Poewe W, et al. A randomized, double-blind, placebo-controlled, delayed start study to assess rasagiline as a disease modifying therapy in Parkinson's disease (the ADAGIO study): rationale, design, and baseline characteristics. Mov Disord 2008; 23: 2194-201.
139. Chan P, Qin Z, Zheng Z, Zhang L, Fang X, Sun F, et al. A Randomized, Double-Blind, Placebo Controlled, Delayed Start Study to Assess Safety, Tolerability and Efficacy of Green Tea Polyphenols in Parkinson's Disease. "XVIII WFN World Congress on Parkinson's Disease and Related Disorders" Miami Beach, FL, USA, December 13-16, 2009.
140. Hendrix, C. Cocktail for modulation of Alzheimer's disease. US20110275591 (2011).
141. Parachikova A, Green KN, Hendrix C, LaFerla FM. Formulation of a medical food cocktail for Alzheimer's disease: beneficial effects on cognition and neuropathology in a mouse model of the disease. PLoS One 2010; 5: e14015.
142. Shytle, R., Jun, T. Green tea polyphenol alpha secretase enhancers and methods of use. US20100040558 (2006).
143. Canto C, Auwerx J. Targeting sirtuin 1 to improve metabolism: all you need is NAD(+)? Pharmacol Rev 2012; 64: 166-87.
144. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 2006; 127: 1109-22.
145. Sinclair D. Diagnostic method for neurodegenerative diseases based on measurement of SIRT1 levels or activity US20050074374 (2005).
146. Magistretti MJ, Bombardelli E. Pharmaceutical compositions containing flavanolignans and phospholipids active principles that combines herbal extracts bound to soybean phospholipids (lecithin). US No-EPO209037 (1987).
147. Pietta P, Simonetti P, Gardana C, Brusamolino A, Morazzoni P, Bombardelli E. Relationship between rate and extent of catechin absorption and plasma antioxidant status. Biochem Mol Biol Int 1998; 46: 895-903.