Potential role of (-)-epigallocatechin-3-gallate (EGCG) in the secondary prevention of Alzheimer disease

Current Drug Targets

Volumn 18, Issue 2, 2017, Pages 174-195

  Xicota, Laura ^a,b,c   Rodríguez Morató, Jose ^a,b,d   Dierssen, Mara ^b,c,e   de la Torre, Rafael ^a,b,d  

^a HOSPITAL DEL MAR   (Spain)

^b UNIVERSITAT POMPEU FABRA   (Spain)

^c CENTRE FOR GENOMIC REGULATION CRG   (Spain)

^d Instituto de Salud Carlos III   (Spain)

^e CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS CIBERER   (Spain)

Author keywords

( ) epigallocatechin 3 gallate; Alzheimer disease; Green tea; Neurodegenerative diseases; Neuroprotection; Oxidative stress

Indexed keywords

CATECHIN; EPIGALLOCATECHIN GALLATE; NEUROPROTECTIVE AGENT;

ALZHEIMER DISEASE; ANALOGS AND DERIVATIVES; ANIMAL; CLINICAL TRIAL (TOPIC); DISEASE MODEL; DRUG EFFECTS; HUMAN; OXIDATIVE STRESS; SECONDARY PREVENTION; TREATMENT OUTCOME;

ALZHEIMER DISEASE; ANIMALS; CATECHIN; CLINICAL TRIALS AS TOPIC; DISEASE MODELS, ANIMAL; HUMANS; NEUROPROTECTIVE AGENTS; OXIDATIVE STRESS; SECONDARY PREVENTION; TREATMENT OUTCOME;

EID: 85011044792     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/1389450116666150825113655     Document Type: Review

References (136)

1. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006; 443 (7113): 787-95.
2. Lagouge M, Larsson NG. The role of mitochondrial DNA mutations and free radicals in disease and ageing. J Intern Med 2013; 273 (6): 529-43.
3. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol 1956; 11 (3): 298-300.
4. Harman D. Origin and evolution of the free radical theory of aging: a brief personal history, 1954-2009. Biogerontology 2009; 10 (6): 773-81.
5. Halliwell B. Free radicals and antioxidants: updating a personal view. Nutr Rev 2012; 70 (5): 257-65.
6. Atwood CS, Obrenovich ME, Liu T, et al. Amyloid-β: a chameleon walking in two worlds: a review of the trophic and toxic properties of amyloid-β. Brain Res Rev 2003; 43 (1): 1-16.
7. Hensley K, Hall N, Subramaniam R, et al. Brain regional correspondence between Alzheimer’s disease histopathology and biomarkers of protein oxidation. J Neurochem 1995; 65 (5): 2146-56.
8. Barnham KJ, Masters CL Bush AI. Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 2004; 3 (3): 205-14.
9. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006; 97 (6), 1634-1658.
10. Halliwell B. Free radicals and antioxidants: a personal view. Nutr Rev 1994; 52 (8): 253-65.
11. Böhm F, Edge R, McGarvey DJ, Truscott TG. β-Carotene with vitamins E and C offers synergistic cell protection against NOx. FEBS Letters, 1998; 436 (3): 387-9.
12. Auten RL, Davis JM. Oxygen toxicity and reactive oxygen species: the devil is in the details. Pediatr Res 2009; 66 (2): 121-7.
13. Klann E. Cell-permeable scavengers of superoxide prevent longterm potentiation in hippocampal area CA1. J Neurophysiol 1998; 80 (1): 452-7.
14. Gahtan E, Auerbach JM, Groner Y, Segal M. Reversible impairment of long-term potentiation in transgenic Cu/Zn-SOD mice. Eur J Neurosci 1998; 10 (2): 538-44.
15. Serrano F, Klann E. Reactive oxygen species and synaptic plasticity in the aging hippocampus. Ageing Res Rev 2004; 3 (4): 431-43.
16. Jack CR. Jr. Alzheimer disease: new concepts on its neurobiology and the clinical role imaging will play. Radiology 2012; 263 (2): 344-61.
17. Valls-Pedret C, Lamuela-Raventós RM, Medina-Remón A, et al. Polyphenol-rich foods in the Mediterranean diet are associated with better cognitive function in elderly subjects at high cardiovascular risk. J Alzheimers Dis 2012; 29 (4): 773-82.
18. Goedert M, Spillantini MG. A century of Alzheimer’s disease. Science 2006; 314 (5800): 777-81.
19. World Alzheimer Report 2009. http: //www.alz.co.uk/ research/files/WorldAlzheimerReport.pdf (June 2015).
20. Wortmann M. Dementia: a global health priority-highlights from an ADI and World Health Organization report. Alzheimers Res Ther 2012; 4 (5): 40.
21. Alzheimer A. Über eine eigenartige Erkankung der Hirnrinde. All Z Psychiatr 1907; 64: 146-8.
22. Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR. An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde". Clin Anat 1995; 8 (6): 429-31.
23. Bertram L, Tanzi RE. Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008; 9 (10): 768-78.
24. Piaceri I, Rinnoci V, Bagnoli S, Failli Y, Sorbi S. Mitochondria and Alzheimer’s disease. J Neurol Sci 2012; 322 (1–2): 31-4.
25. Verghese PB, Castellano JM, Holtzman DM. Apolipoprotein E in Alzheimer’s disease and other neurological disorders. Lancet Neurol 2011; 10 (3): 241-52.
26. Fuster-Matanzo A, Llorens-Martin M, Hernandez F, Avila J. Role of neuroinflammation in adult neurogenesis and Alzheimer disease: therapeutic approaches. Mediators Inflamm 2013; 260925.
27. Niranjan R. Molecular basis of etiological implications in Alzheimer’s disease: focus on neuroinflammation. Mol Neurobiol 2013; 48 (3): 412-28.
28. Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev 2011; 35 (6): 1397-409.
29. Bartus RT, Dean RL 3rd; Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217 (4558): 408-14.
30. Coyle JT, Price DL, DeLong MR. Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 1983; 219 (4589): 1184-90.
31. Kessels HW, Nabavi S, Malinow R. Metabotropic NMDA receptor function is required for beta-amyloid-induced synaptic depression. Proc Natl Acad Sci USA 2013; 110 (10): 4033-8.
32. Ferreira ST, Vieira MN, De Felice FG. Soluble protein oligomers as emerging toxins in Alzheimer’s and other amyloid diseases. IUBMB Life 2007; 59 (4-5): 332-45.
33. Nalivaeva NN, Turner AJ. The amyloid precursor protein: A biochemical enigma in brain development, function and disease. FEBS Lett 2013, 587 (13): 2046-54.
34. Haass C, Kaether C, Thinakaran G, Sisodia S. Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med 2012; 2 (5): a006270.
35. Postina R. Activation of α-secretase cleavage. J Neurochem 2012; 120 (Suppl 1): 46-54.
36. Mu Y, Gage FH. Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener 2011; 6: 85.
37. Webb RL, Murphy MP. β-Secretases, Alzheimer’s disease, and down syndrome. Curr Gerontol Geriatr Res 2012; 2012: 362839.
38. Acquati F, Accarino M, Nucci C, et al. The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the Down critical region. FEBS Lett 2000; 468 (1): 59-64.
39. Azkona G, Amador-Arjona A, Obradors-Tarragó C, et al. Characterization of a mouse model overexpressing beta-site APPcleaving enzyme 2 reveals a new role for BACE2. Genes Brain Behav 2010; 9 (2): 160-72.
40. Shi XP, Tugusheva K, Bruce JE, et al. Beta-secretase cleavage at amino acid residue 34 in the amyloid beta peptide is dependent upon gamma-secretase activity. J Biol Chem 2003; 278 (23): 21286-94.
41. Azkona G, Levannon D, Groner Y, Dierssen M. In vivo effects of APP are not exacerbated by BACE2 co-overexpression: behavioural characterization of a double transgenic mouse model. Amino Acids 2010; 39 (5): 1571-80.
42. Sun X, He G, Song W. BACE2, as a novel APP θ-secretase, is not responsible for the pathogenesis of Alzheimer’s disease in Down syndrome. The FASEB Jl 2006; 20 (9): 1369-76.
43. Cavallucci V, D’Amelio M, Cecconi F. Abeta toxicity in Alzheimer’s disease. Mol Neurobiol 2012; 45 (2): 366-78.
44. De Felice FG. Alzheimer’s disease and insulin resistance: translating basic science into clinical applications. J Clin Invest 2013; 123 (2): 531-9.
45. de la Torre R, Dierssen M. Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and future. Prog Brain Res 2012; 197, 1-14.
46. Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci 2012; 13 (12): 844-58.
47. Rafii MS. The pulse of drug development for Alzheimer’s disease. Rev Recent Clin Trials 2010; 5 (1): 57-62.
48. Cheon MS, Dierssen M, Kim SH, Lubec G. Protein expression of BACE1, BACE2 and APP in Down syndrome brains. Amino Acids 2008; 35 (2): 339-43.
49. Ferrer I, Barrachina M, Puig B, et al. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol Dis 2005; 20 (2): 392-400.
50. Ryoo SR, Cho HJ, Lee HW, et al. Dual-specificity tyrosine (Y)-phosphorylation regulated kinase 1A-mediated phosphorylation of amyloid precursor protein: evidence for a functional link between Down syndrome and Alzheimer’s disease. J Neurochem 2008; 104 (5): 1333-44.
51. Walte A, Rüben K, Birner-Gruenberger R, et al. Mechanism of dual specificity kinase activity of DYRK1A. FEBS J 2013; 280 (18): 4495-511.
52. Ryu YS, Park SY, Jung MS, et al. Dyrk1A-mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer’s disease. J Neurochem 2010; 115 (3): 574-84.
53. Kimura R, Kamino K, Yamamoto M, et al. The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease. Hum Mol Genet 2007; 16 (1): 15-23.
54. Haas C. Strategies, development, and pitfalls of therapeutic options for Alzheimer’s disease. J Alzheimers Dis 2012; 28 (2): 241-81.
55. Castellani RJ, Nunomura A, Lee HG, Perry G, Smith MA. Phosphorylated tau: toxic, protective, or none of the above. J Alzheimers Dis 2008; 14 (4): 377-83.
56. Walker LC, Diamond MI, Duff KE, Hyman BT. Mechanisms of protein seeding in neurodegenerative diseases. JAMA Neurol 2013; 70 (3): 304-10.
57. Barnham KJ, Masters CL, Bush AI. Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 2004; 3 (3): 205-14.
58. Nunomura A, Perry G, Aliev G, et al. Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 2001; 60 (8): 759-67.
59. Zarkovic K. 4-hydroxynonenal and neurodegenerative diseases. Mol Aspects Med 2003; 24 (4-5), 293-303.
60. Butterfield DA, Castegna A, Lauderback CM, Drake J. Evidence that amyloid beta-peptide-induced lipid peroxidation and its sequelae in Alzheimer’s disease brain contribute to neuronal death. Neurobiol Aging, 2002; 23 (5): 655-64.
61. Gandhi S, Abramov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012; 2012, 428010.
62. Selley ML, Close DR, Stern SE. The effect of increased concentrations of homocysteine on the concentration of (E)-4-hydroxy-2-nonenal in the plasma and cerebrospinal fluid of patients with Alzheimer’s disease. Neurobiol Aging 2002; 23 (3): 383-88.
63. Gabbita SP, Lovell MA, Markesbery WR. Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J Neurochem 1998; 71 (5): 2034-40.
64. Lovell MA, Gabbita SP, Markesbery WR. Increased DNA oxidation and decreased levels of repair products in Alzheimer’s disease ventricular CSF. J Neurochem 1999; 72, (2): 771-6.
65. Shan X, Tashiro H, Lin CL. The identification and characterization of oxidized RNAs in Alzheimer’s disease. J Neurosci 2003; 23 (12): 4913-21.
66. Singh M, Dang TN, Arseneault M, Ramassamy C. Role of byproducts of lipid oxidation in Alzheimer’s disease brain: a focus on acrolein. J Alzheimers Dis 2010; 21 (3): 741-56.
67. Iulita MF, Cuello AC. Nerve growth factor metabolic dysfunction in Alzheimer’s disease and Down syndrome. Trends Pharmacol Sci 2014; 35 (7): 338-48.
68. Perry EK, Johnson M, Ekonomou A. et al., Neurogenic abnormalities in Alzheimer’s disease differ between stages of neurogenesis and are partly related to cholinergic pathology. Neurobiol Dis 2012, 47 (2): 155-62.
69. Pasinetti GM, Ho L, Dooley C, Abbi B, Lange G. Select noncoding RNA in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF/OIF Veterans. Am J Neurodegener Dis 2012; 1 (1): 88-98.
70. Roberson ED, Mucke L. 100 years and counting: prospects for defeating Alzheimer’s disease. Science 2006, 314 (5800): 781-4.
71. U.S. National Institutes of Health http://www.clinicaltrials.gov/ (June, 2015)
72. Williams RJ, Spencer JP. Flavonoids, cognition, and dementia: actions, mechanisms, and potential therapeutic utility for Alzheimer disease. Free Radic Biol Med 2012; 52 (1): 35-45.
73. Ramassamy C. Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 2006; 545 (1): 51-64.
74. Yang CS, Pan E. The effects of green tea polyphenols on drug metabolism. Expert Opin Drug Metab Toxicol 2012; 8 (6): 677-89.
75. Aron PM, Kennedy JA. Flavan-3-ols: nature, occurrence and biological activity. Mol Nutr Food Res 2008; 52 (1): 79-104.
76. Miller RJ, Jackson KG, Dadd T, et al. A preliminary investigation of the impact of catechol-O-methyltransferase genotype on the absorption and metabolism of green tea catechins. Eur J Nutr 2012; 51 (1): 47-55.
77. Suzuki Y, Miyoshi N, Isemura, M. Health-promoting effects of green tea. Proc Jpn Acad Ser B Phys Biol Sci 2012; 88 (3): 88-101.
78. Kuriyama S, Hozawa A, Ohmori K, et al. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr 2006; 83 (2): 355-61.
79. Meng X, Sang S, Zhu N, et al. Identification and characterization of methylated and ring-fission metabolites of tea catechins formed in humans, mice, and rats. Chem Res Toxicol 2002; 15 (8): 1042-50.
80. Zuo Z, Zhang L, Zhou L. In tea in health and disease prevention; Academic Press 2013; pp 399-412.
81. Sang S, Lambert JD, Ho CT, Yang CS. The chemistry and biotransformation of tea constituents. Pharmacol Res 2011; 64 (2): 87-99.
82. Lu H, Meng X, Li C, et al. Glucuronides of tea catechins: enzymology of biosynthesis and biological activities. Drug Metab Dispos 2003; 31 (4): 452-61.
83. Rio DD, Calani L, Cordero C, et al. Bioavailability and catabolism of green tea flavan-3-ols in humans. Nutrition 2010; 26 (11-12): 1110-6.
84. Lambert JD, Sang S, Yang CS. Biotransformation of green tea polyphenols and the biological activities of those metabolites. Mol Pharm 2007; 4 (6): 819-25.
85. Yang CS, Chen L, Lee MJ, et al. Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev 1998; 7 (4): 351-4.
86. Chow HH, Cai Y, Alberts DS, et al. Phase I pharmacokinetic study of tea polyphenols following single-dose administration of epigallocatechin gallate and polyphenon E. Cancer Epidemiol Biomarkers Prev 2001; 10 (1): 53-8.
87. Suganuma M, Okabe S, Oniyama M, et al. Wide distribution of [3H] (-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 1998; 19 (10): 1771-6.
88. Chu KO, Wang CC, Chu CY, et al. Determination of catechins and catechin gallates in tissues by liquid chromatography with coulometric array detection and selective solid phase extraction. J Chromatogr B Analyt Technol Biomed Life Sci 2004; 810 (2): 187-95.
89. Yano S, Fujimura Y, Umeda D, et al. Relationship between the biological activities of methylated derivatives of (-)-epigallocatechin-3-O-gallate (EGCG) and their cell surface binding activities. J Agric Food Chem 2007; 55 (17): 7144-8.
90. Lotito SB, Zhang WJ, Yang CS, Crozier A, Frei B. Metabolic conversion of dietary flavonoids alters their anti-inflammatory and antioxidant properties. Free Radic Biol Med 2011; 51 (2): 454-63.
91. Mandel S, Youdim MB. Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases. Free Radic Biol Med 2004; 37 (3): 304-17.
92. Na H-K, Surh Y-J. Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem Toxicol 2008; 46 (4): 1271-8.
93. LaFerla FM, Green KN. Animal models of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2 (11), pii 9006320.
94. Levites Y, Amit T, Mandel S, Youdim MB. Neuroprotection and neurorescue against Abeta toxicity and PKC-dependent release of nonamyloidogenic soluble precursor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. FASEB J 2003; 17 (8): 952-4.
95. Lin CL, Chen TF, Chiu MJ, Way TD, Lin JK. Epigallocatechin gallate (EGCG) suppresses beta-amyloid-induced neurotoxicity through inhibiting c-Abl/FE65 nuclear translocation and GSK3 beta activation. Neurobiol Aging 2009; 30 (1): 81-92.
96. Choi SM, Kim BC, Cho YH, et al. Effects of flavonoid compounds on beta-amyloid-peptide-induced neuronal death in cultured mouse cortical neurons. Chonnam Med J 2014; 50 (2): 45-51.
97. He Y, Cui J, Lee JC, et al. Prolonged exposure of cortical neurons to oligomeric amyloid-beta impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (-)-epigallocatechin-3-gallate. ASN Neuro 2011; 3 (1): e00050.
98. Zhang X, Wu M, Lu F, et al. Involvement of alpha7 nAChR signaling cascade in epigallocatechin gallate suppression of betaamyloid-induced apoptotic cortical neuronal insults. Mol Neurobiol 2014; 49 (1): 66-77.
99. Haque AM, Hashimoto M, Katakura M, Hara Y, Shido O. Green tea catechins prevent cognitive deficits caused by Abeta1-40 in rats. J Nutr Biochem 2008; 19 (9): 619-26.
100. Lee JW, Lee YK, Ban JO, 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 (10): 1987-93.
101. Lee YK, Yuk DY, Lee JW, et al., (-)-Epigallocatechin-3-gallate prevents lipopolysaccharide-induced elevation of beta-amyloid generation and memory deficiency. Brain Res 2009; 1250: 164-74.
102. Walker JM, Klakotskaia D, Ajit D, et al. Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer’s disease mouse model. J Alzheimers Dis 2015; 44 (2): 561-72.
103. Reznichenko L, Amit T, Youdim MB, Mandel S. Green tea polyphenol (-)-epigallocatechin-3-gallate induces neurorescue of long-term serum-deprived PC12 cells and promotes neurite outgrowth. J Neurochem 2005; 93 (5): 1157-1167.
104. Arendash GW, Lewis J, Leighty RE, et al. Multi-metric behavioral comparison of APPsw and P301L models for Alzheimer’s disease: linkage of poorer cognitive performance to tau pathology in forebrain. Brain Res 2004; 1012 (1-2): 29-41.
105. Rezai-Zadeh K, Arendash GW, Hou H, 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.
106. Li Q, Zhao HF, Zhang ZF, et al. Long-term administration of green tea catechins prevents age-related spatial learning and memory decline in C57BL/6 J mice by regulating hippocampal cyclic ampresponse element binding protein signaling cascade. Neuroscience 2009; 159 (4): 1208-15.
107. Li Q, Zhao HF, Zhang ZF, et al. Long-term 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. Neuroscience 2009; 163 (3): 741-749.
108. Jia N, Han K, Kong JJ, et al. (-)-Epigallocatechin-3-gallate alleviates spatial memory impairment in APP/PS1 mice by restoring IRS-1 signaling defects in the hippocampus. Mol Cell Biochem 2013.
109. Liu M, Chen F, Sha L, et al. (-)-Epigallocatechin-3-Gallate Ameliorates Learning and Memory Deficits by Adjusting the Balance of TrkA/p75 Signaling in APP/PS1 Transgenic Mice. Mol Neurobiol 2013.
110. Wang Y, Li M, Xu X, et al. Green tea epigallocatechin-3-gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis. Mol Nutr Food Res 2012; 56 (8): 1292-1303.
111. Biasibetti R, Tramontina AC, Costa AP, et al, Green tea (-) epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia. Behav Brain Res 2013; 236 (1): 186-93.
112. Lee YJ, Choi DY, Yun YP, et al. Epigallocatechin-3-gallate prevents systemic inflammation-induced memory deficiency and amyloidogenesis via its anti-neuroinflammatory properties. J Nutr Biochem 2013; 24 (1): 298-310.
113. Villarreal A, Reyes RXA, Angelo MF, Reines AG, Ramos AJ. S100B alters neuronal survival and dendrite extension via RAGEmediated NF-kappaB signaling. J Neurochem 2011; 117 (2): 321-32.
114. Rezai-Zadeh K, Shytle D, Sun N, 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 (38): 8807-14.
115. Reznichenko L, Amit T, Zheng H, et al. Reduction of ironregulated 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 (2): 527-36.
116. Obregon DF, Rezai-Zadeh K, Bai Y, et al. ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alphasecretase cleavage of amyloid precursor protein. J Biol Chem 2006; 281 (24): 16419-27.
117. Fernandez JW, Rezai-Zadeh K, Obregon D, Tan J. EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP. FEBS Lett 2010, 584 (19): 4259-67.
118. 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 (13): 1329-33.
119. Rushworth JV, Griffiths HH, Watt NT, Hooper NM. Prion proteinmediated toxicity of amyloid-beta oligomers requires lipid rafts and the transmembrane LRP1. J Biol Chem 2013; 288 (13): 8935-51.
120. Adayev T, Chen-Hwang MC, Murakami N, Wegiel J, Hwang YW. Kinetic properties of a MNB/DYRK1A mutant suitable for the elucidation of biochemical pathways. Biochemistry 2006; 45 (39): 12011-19.
121. Guedj F, Sebrie C, Rivals I, et al. Green tea polyphenols rescue of brain defects induced by overexpression of DYRK1A. PLoS One 2009, 4 (2): e4606.
122. Romeo L, Intrieri M, D’Agata V, et al. The major green tea polyphenol, (-)-epigallocatechin-3-gallate, induces heme oxygenase in rat neurons and acts as an effective neuroprotective agent against oxidative stress. J Am Coll Nutr 2009, 28 Suppl, 492S-9S.
123. Scapagnini G, Vasto S, Abraham NG, et al. Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders. Mol Neurobiol 2011; 44 (2): 192-201.
124. Na HK, Kim EH, Jung JH, et al. (-)-Epigallocatechin gallate induces Nrf2-mediated antioxidant enzyme expression via activation of PI3K and ERK in human mammary epithelial cells. Arch Biochem Biophys 2008; 476 (2): 171-7.
125. Na HK, Surh YJ. Modulation of Nrf2-mediated antioxidant and detoxifying enzyme induction by the green tea polyphenol EGCG. Food Chem Toxicol 2008; 46 (4): 1271-8.
126. Cheng X, Ku CH, Siow RC. Regulation of the Nrf2 antioxidant pathway by microRNAs: New players in micromanaging redox homeostasis. Free Radic Biol Med 2013; 64 4-11.
127. Khan SI, Aumsuwan P, Khan IA, Walker LA, Dasmahapatra AK. Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome. Chem Res Toxicol 2012; 25 (1): 61-73.
128. Kim YS, Farrar W, Colburn NH, Milner JA. Cancer stem cells: potential target for bioactive food components. J Nutr Biochem 2012; 23 (7): 691-8.
129. 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 (2): 217-23.
130. Unno K, Takabayashi F, Kishido T, Oku N. Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp Gerontol 2004; 39 (7): 1027-34.
131. Unno K, Takabayashi F, Yoshida H, et al. Daily consumption of green tea catechin delays memory regression in aged mice. Biogerontology 2007; 8 (2): 89-95.
132. Gundimeda U, McNeill TH, Fan TK, et al. Green tea catechins potentiate the neuritogenic action of brain-derived neurotrophic factor: role of 67-kDa laminin receptor and hydrogen peroxide. Biochem Biophys Res Commun 2014; 445 (1): 218-24.
133. Mahler A, Steiniger J, Bock M, et al. Metabolic response to epigallocatechin-3-gallate in relapsing-remitting multiple sclerosis: a randomized clinical trial. Am J Clin Nutr 2015; 101 (3): 487-95.
134. Kristen AV, Lehrke S, Buss S, et al. Green tea halts progression of cardiac transthyretin amyloidosis: an observational report. Clin Res Cardiol 2012; 101 (10): 805-13.
135. Park SK, Jung IC, Lee WK, et al. A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study. J Med Food 2011; 14 (4): 334-43.
136. Chow HH, Cai Y, Hakim IA, et al. Pharmacokinetics and safety of green tea polyphenols after multiple-dose administration of epigallocatechin gallate and polyphenon E in healthy individuals. Clin Cancer Res 2003; 9 (9): 3312-9.