Examining the potential clinical value of curcumin in the prevention and diagnosis of Alzheimer's disease

British Journal of Nutrition

Volumn 115, Issue 3, 2016, Pages 449-465

  Goozee, K G ^a,b,d   Shah, T M ^b,c   Sohrabi, H R ^b,c   Rainey Smith, S R ^b,c   Brown, B ^b,c   Verdile, G ^b,c,d,e   Martins, R N ^a,b,c,d  

^a McCusker KARVIAH Research Centre   (Australia)

^b EDITH COWAN UNIVERSITY   (Australia)

^c HOLLYWOOD PRIVATE HOSPITAL   (Australia)

^d UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^e CURTIN UNIVERSITY   (Australia)

Author keywords

Alzheimer's disease; Amyloid; Curcumin; Retinal imaging

Indexed keywords

1,7 BIS(4' HYDROXY 3' TRIFLUOROMETHOXYPHENYL) 4 METHOXYCARBONYLETHYL 1,6 HEPTADIENE 3,5 DIONE; 4,4' [(1 PHENYL 1H PYRAZOLE 3,5 DIYL)DIETHENE 2,1 DIYL]BIS(2 METHOXYPHENOL); 5 (4 HYDROXYPHENYL) 3 OXO PENTANOIC ACID [2 (5 METHOXY1H NDOL 3 YL)ETHYL]AMIDE; ACETYLCHOLINESTERASE; AMYLOID BETA PROTEIN; CURCUMIN; FLUOROCHROME; MELATONIN; PROTEASOME; TELOMERASE; UNCLASSIFIED DRUG; FLUORESCENT DYE; NEUROPROTECTIVE AGENT; NOOTROPIC AGENT;

ALZHEIMER DISEASE; ARTICLE; BLOOD BRAIN BARRIER; COGNITION; DIET SUPPLEMENTATION; DIETARY INTAKE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG FORMULATION; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; EPIGENETICS; HUMAN; IN VIVO STUDY; LIPID METABOLISM; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PROTEIN AGGREGATION; PROTEIN DEGRADATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETINA; UNSPECIFIED SIDE EFFECT; ANIMAL; DISEASE MODEL; DRUG EFFECTS; METABOLISM; NEUROFIBRILLARY TANGLE; PROCEDURES; RADIOASSAY;

ALZHEIMER DISEASE; ANIMALS; COGNITION; CURCUMIN; DISEASE MODELS, ANIMAL; FLUORESCENT DYES; HUMANS; NEUROFIBRILLARY TANGLES; NEUROPROTECTIVE AGENTS; NOOTROPIC AGENTS; RADIOLIGAND ASSAY; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84955179058     PISSN: 00071145     EISSN: 14752662     Source Type: Journal    
DOI: 10.1017/S0007114515004687     Document Type: Article

References (191)

1. Prince M, Jackson J (editors) (2009) Alzheimer's Disease International: World Alzheimer Report. Executive Summary. London: Alzheimer's Disease International.
2. Lee VM, Goedert M, Trojanowski JQ (2001) Neurodegenerative tauopathies. Annu Rev Neurosci 24, 1121-1159.
3. Frost S, Kanagasingam Y, Macaulay L, et al. (2014) Retinal amyloid fluorescence imaging predicts cerebral amyloid burden and Alzheimer's disease (oral presentation). Alzheimers Dement 10, 234-235.
4. Ittner LM, Götz J (2011) Amyloid-and tau-a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci 12, 67-72.
5. Ittner LM, Ke YD, Delerue F, et al. (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 142, 387-397.
6. Krishnaswamy K, Verdile G, Groth DM, et al. (2009) The structure and function of Alzheimer's gamma secretase enzyme complex. Crit Rev Clin Lab Sci 46, 282-301.
7. Villemagne VL, Burnham S, Bourgeat P, et al. (2013) Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol 12, 357-367.
8. Walsh DM, Teplow DB (2012) Alzheimer's disease and the amyloid beta-protein. Progr Mol Biol Transl Sci 107, 101-124.
9. O'Malley T, Oktaviani N, Zhang D, et al. (2014) A beta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies. Biochem J 461, 413-426.
10. McKhann GM, Knopman DS, Chertkow H, et al. (2011) The diagnosis of dementia due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7, 263-269.
11. Majeed M, Badmaev V, Murrary F (1996) Turmeric and the Healing Curcuminoids. New Canaan, CT: Keats Publishing Inc.
12. Kelloff GJ, Crowell JA, Steele VE, et al. (2000) Progress in cancer chemoprevention: development of diet-derived chemopreventive agents. J Nutr 130, 467S-471S.
13. Goel A, Kunnumakkara AB, Aggarwal BB (2008) Curcumin as 'Curecumin': from kitchen to clinic. Biochem Pharmacol 75, 787-809.
14. Ammon HP, Wahl MA (1991) Pharmacology of Curcuma longa. Plata Med 57, 107.
15. Begum AN, Jones MR, Lim GP, et al. (2008) Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther 326, 196-208.
16. Zhou H, Beevers CS, Huang S (2011) Targets of curcumin. Curr Drug Targets 12, 332-347.
17. Milobedeska J, Kostanecki V, Lampe V (1910) Structure of curcumin. Berichte der Deutschen Chemischen Gesellschaft 43, 2163-2170.
18. Hamaguchi T, Ono K, Yamada M (2010) Review: curcumin and Alzheimer's disease. CNS Neurosci Ther 16, 285-297.
19. Agarwal DK, Mishra PK (2010) Curcumin and its analogues: potential anticancer agents. Med Res Rev 30, 818-860.
20. Mishra S, Palanivelu K (2008) The effect of curcumin (turmeric) on Alzheimer's disease: an overview. Ann Indian Acad Neurol 11, 13-19.
21. Basnet P, Skalko-Basnet N (2011) Curcumin: an antiinflammatory molecule from a curry spice on the path to cancer treatment. Molecules 16, 4567-4598.
22. Pan MH, Lin-Shiau SY, Lin JK (2000) Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. Biochem Pharmacol 60, 1665-1676.
23. Xu YX, Pindolia KR, Janakiraman N, et al. (1997) Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NFkB DNA-binding activity in bone marrow stromal cells. Hematopathol Mol Hematol 11, 49-62.
24. Zhang C, Browne A, Child D, et al. (2010) Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. J Biol Chem 285, 28472-28480.
25. Joe B, Rao UJSP, Lokesh BR (1997) Presence of an acidic glycoprotein in the serum of arthritic rats: modulation by capsaicin and curcumin. Mol Cell Biochem 169, 125-134.
26. Jackson JK, Higo T, Hunter WL, et al. (2006) The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res 55, 168-175.
27. Hanai H, Sugimoto K (2009) Curcumin has bright prospects for the treatment of inflammatory bowel disease. Curr Pharm Des 15, 2087-2094.
28. Kurd SK, Smith N, VanVoorhees A, et al. (2008) Oral curcumin in the treatment of moderate to severe psoriasis vulgaris: a prospective clinical trial. J Am Acad Dermatol 58, 625-631.
29. Thangapazham RL, Sharma A, Maheshwari RK (2007) Beneficial role of curcumin in skin diseases. Adv Exp Med Biol 595, 343-357.
30. Tsui KH, Feng TH, Lin CM, et al. (2008) Curcumin blocks the activation of androgen and interlukin-6 on prostate-specific antigen expression in human prostatic carcinoma cells. J Androl 29, 661-668.
31. Liu D, Chen Z (2013) The effect of curcumin on breast cancer cells. J Breast Cancer 16, 133-137.
32. Friedman L, Lin L, Ball S, et al. (2009) Curcumin analogues exhibit enhanced growth suppressive activity in human pancreatic cancer cells. Anticancer Drugs 20, 444-449.
33. Lim TG, Lee SY, Huang Z, et al. (2014) Curcumin suppresses proliferation of colon cancer cells by targeting CDK2. Cancer Prev Res (Phila) 7, 466-474.
34. Jackson-Bernitsas DG, Ichikawa H, Takada Y, et al. (2007) Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kappaB activation and proliferation in human head and neck squamous cell carcinoma. Oncogene 26, 1385-1397.
35. Zhao BL, Li XJ, He RG, et al. (1989) Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals. Cell Biophys 14, 175-185.
36. Martins RN, Harper CG, Stokes GB, et al. (1986) Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer's disease may reflect oxidative stress. J Neurochem 46, 1042-1045.
37. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356.
38. Huang HC, Jiang ZF (2009) Accumulated amyloid-peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer's disease. J Alzheimers Dis 16, 15-27.
39. Huang HC, Chang P, Dai XL, et al. (2012) Protective effects of curcumin on amyloid-beta-induced neuronal oxidative damage. Neurochem Res 37, 1584-1597.
40. Garcia-Alloza M, Borrelli LA, Rozkalne A, et al. (2007) Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 102, 1095-1104.
41. Mutsuga M, Chambers JK, Uchida K, et al. (2012) Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer's brain. J Vet Med Sci 74, 51-57.
42. Kosik KS, Joachim CL, Selkoe DJ (1986) Microtubuleassociated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc Natl Acad Sci USA 83, 4044-4048.
43. Glenner GG, Wong CW (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerevrovascular amyloid protein. Biochem Biophys Res Commun 120, 885-890.
44. Masters CL, Multhaup G, Simms G, et al. (1985b) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4, 2757-2763.
45. Villemagne VL, Rowe CC (2013) Long night's journey into the day: amyloid-beta imaging in Alzheimer's disease. J Alzheimers Dis 33, Suppl. 1, S349-S359.
46. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid beta-peptide. Nat Rev Mol Cell Biol 8, 101-112.
47. Manczak M, Mao P, Calkins MJ, et al. (2010) Mitochondriatargeted antioxidants protect against amyloid-beta toxicity in Alzheimer's disease neurons. J Alzheimers Dis 20, Suppl. 2, S609-S631.
48. Cash DM, Liang Y, Ryan NS, et al. (2013) The pattern of atrophy in familial alzheimer disease: volumetric MRI results from the DIAN study. Neurology 81, 1425-1433.
49. Chetelat G, Villemagne VL, Villain N, et al. (2012) Accelerated cortical atrophy in cognitively normal elderly with high beta-amyloid deposition. Neurology 78, 477-484.
50. Chetelat G, Villemagne VL, Pike KE, et al. (2011) Independent contribution of temporal beta-amyloid deposition to memory decline in the pre-dementia phase of Alzheimer's disease. Brain 134, 798-807.
51. Reddy PH, Tripathi R, Troung Q, et al. (2012) Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: implications to mitochondria-targeted antioxidant therapeutics. Biochim Biophys Acta 1822, 639-649.
52. Ferreira ST, Klein WL (2011) The A oligomer hypothesis for synapse failure and memory loss in Alzheimer's disease. Neurobiol Learn Mem 96, 529-543.
53. Zhao J, Luo Y, Jang H, et al. (2012) Probing ion channel activity of human islet amyloid polypeptide (amylin). Biochim Biophys Acta 1818, 3121-3130.
54. Johnson E, Brookmeyer R, Ziegler-Graham K (2007) Modeling the effect of Alzheimer's disease on mortality. Int J Biostat 3, Article 13, 12-21.
55. Brookmeyer R, Gray S, Kawas C (1998) Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health 88, 1337-1342.
56. Vickland V, Morris T, Draper B, et al. (2012) Modelling the Impact of Interventions to Delay the Onset of Dementia in Australia. Report for Alzheimers Australia. Sydney, Australia: Alzheimer's Australia Inc.
57. Bieschke J, Herbst M, Wiglenda T, et al. (2012) Small-molecule conversion of toxic oligomers to nontoxic-sheet-rich amyloid fibrils. Nat Chem Biol 8, 93-101.
58. Ono K, Hasegawa K, Naiki H, et al. (2004) Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J Neurosci Res 75, 742-750.
59. Reinke AA, Gestwicki JE (2007) Structure-activity of amyloid betta-aggregation inhibitors based on curcumin: influence of linker length and flexibility. Chem Biol Drug Des 70, 206-215.
60. Yang F, Lim GP, Begum AN, et al. (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280, 5892-5901.
61. Ghalebani L, Wahlstrom A, Danielsson J, et al. (2012) pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-peptide. Biochem Biophys Res Commun 421, 554-560.
62. Faller P, Hureau C (2012) A bioinorganic view of Alzheimers disease: when misplaced metal ions (Re)direct the electrons to the wrong target. Chemistry 18, 15910-15920.
63. Banerjee R (2014) Effect of curcumin on the metal ion induced fibrillization of amyloid-peptide. Spectrochim Acta A Mol Biomol Spectrosc 117, 798-800.
64. Kochi A, Lee HJ, Vithanarachchi SM, et al. (2015) Inhibitory activity of curcumin derivatives towards metal-free and metal-induced amyloid-beta aggregation. Curr Alzheimer Res 12, 415-423.
65. Fu Z, Aucoin D, Ahmed M, et al. (2014) Capping of a42 oligomers by small molecule inhibitors. Biochemistry 53, 7893-7903.
66. Mithu VS, Sarkar B, Bhowmik D, et al. (2014) Curcumin alters the salt bridge-containing turn region in amyloid (1-42) aggregates. J Biol Chem 289, 11122-11131.
67. Caesar I, Jonson M, Nilsson K, et al. (2012) Curcumin promotes A fibrillation and reduces neurotoxicity in transgenic drosophila (reduced neurotoxicity by promoted fibrillation). PLOS ONE 7, e31424.
68. Liu H, Li Z, Qiu D, et al. (2010) The inhibitory effects of different curcuminoids on-amyloid protein,-amyloid precursor protein and-site amyloid precursor protein cleaving enzyme 1 in swAPP HEK293 cells. Neurosci Lett 485, 83-88.
69. Shimmyo Y, Kihara T, Akaike A, et al. (2008) Epigallocatechin-3-gallate and curcumin suppress amyloid beta-induced beta-site APP cleaving enzyme-1 upregulation. Neuroreport 19, 1329-1333.
70. Li Y, Zhang X, Si L (2009) Curcumin reduces A beta generation by PPAR gamma activation and BACE1 inhibition in vitro. J Neurochem 110, 61.
71. Wang X, Kim JR, Lee SB, et al. (2014) Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer's disease Drosophila models. BMC Complement Altern Med 14, 88-88.
72. Sathya M, Premkumar P, Karthick C, et al. (2012) BACE1 in Alzheimer's disease. Clin Chim Acta 414, 171-178.
73. Jiaranaikulwanitch J, Govitrapong P, Fokin VV, et al. (2012) From BACE1 inhibitor to multifunctionality of tryptoline and tryptamine triazole derivatives for Alzheimer's disease. Molecules 17, 8312-8333.
74. Lin R, Chen X, Li W, et al. (2008) Exposure to metal ions regulates mRNA levels of APP and BACE1 in PC12 cells: blockage by curcumin. Neurosci Lett 440, 344-347.
75. Park SY, Kim HS, Cho EK, et al. (2008) Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Food Chem Toxicol 46, 2881-2887.
76. Kim DS, Park SY, Kim JK (2001) Curcuminoids from Curcuma longa L (Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from beta A(1-42) insult. Neurosci Lett 303, 57-61.
77. Shi X, Zheng Z, Li J, et al. (2015) Curcumin inhibits Abeta-induced microglial inflammatory responses in vitro: involvement of ERK1/2 and p38 signaling pathways. Neurosci Lett 594, 105-110.
78. Zhang X, Yin WK, Shi XD, et al. (2011) Curcumin activates Wnt/-catenin signaling pathway through inhibiting the activity of GSK-3B in APPswe transfected SY5Y cells. Eur J Pharm Sci 42, 540-546.
79. Olivia CA, Vargas JY, Inestrosa NC (2013) Wnt signaling: role in LTP, neural networks and memory. Ageing Res Rev 12, 786-800.
80. Purro SA, Dickins EM, Salinas PC (2012) The secreted Wnt antagonist Dickkopf-1 is required for amyloid B-medicated synaptic loss. J Neurosci 32, 3492-3498.
81. Wan W, Xia S, Kalionis B, et al. (2014) The role of Wnt signaling in the development of Alzheimer's disease: a potential therapeutic target. Biomed Res Int 2014, 1-9.
82. Parr C, Mirzaei N, Christian M (2015) Activation of the Wnt/beta-catenin pathway represses the transcription of the beta-amyloid precursor protein cleaving enzyme (BACE-1) via binding of T-cell factor-4 to BACE1 promoter. FASEB J 29, 623-635.
83. Khan MA, Akhtar N, Sharma V, et al. (2015) Product development studies on sonocrystallized curcumin for the treatment of gastric cancer. Pharmaceutics 7, 43-63.
84. Bates KA, Verdile G, Li QX, et al. (2009) Clearance mechanisms of Alzheimer's amyloid-beta peptide: implications for therapeutic design and diagnostic tests. Mol Psychiatry 14, 469-486.
85. Foster JK, Verdile G, Bates KA, et al. (2009) Immunization in Alzheimer's disease: naive hope or realistic clinical potential Mol Psychiatry 14, 239-251.
86. Fiala M, Lin J, Ringman J, et al. (2005) Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer's disease patients. J Alzheimers Dis 7, 221-232.
87. Zhang L, Fiala M, Cashman J, et al. (2006) Curcuminoids enhance amyloid-beta uptake by macrophages of Alzheimer's disease patients. J Alzheimers Dis 10, 1-7.
88. Fiala M, Liu PT, Espinosa-Jeffrey A, et al. (2007) Innate immunity and transcription of MGAT-II and toll-like receptors in Alzheimer's disease patients are improved by bisdemethoxycurcumin. Proc Natl Acad Sci USA 104, 12849-12854.
89. Masoumi A, Goldenson B, Ghirmai S, et al. (2009) 1 alpha,25-Dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-beta clearance by macrophages of Alzheimer's disease patients. J Alzheimers Dis 17, 703-717.
90. Mizwicki MT, Menegaz D, Barrientos-Durán A, et al. (2012) Genomic and nongenomic signaling induced by 1,25(OH) 2-vitamin D3 promotes the recovery of amyloid-phagocytosis by Alzheimer's disease macrophages. J Alzheimers Dis 29, 51-62.
91. Soni KB, Kuttan R (1992) Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol 36, 273-275.
92. Soudamini KK, Unnikrishnan MC, Soni KB, et al. (1992) Inhibition of lipid peroxidation and cholesterol levels in mice by curcumin. Indian J Physiol Pharmacol 36, 239-243.
93. Sreejayan N, Rao MNA (1994) Curcuminoids as potent inhibitors of lipid peroxidation. J Pharm Pharmacol 46, 1013-1016.
94. Peschel D, Koerting R, Nass N (2007) Curcumin induces changes in expression of genes involved in cholesterol homeostasis. J Nutr Biochem 18, 113-119.
95. Feng D, Ohlsson L, Duan RD (2010) Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression. Lipids Health Dis 9, 40-45.
96. Kim M, Kim Y (2010) Hypocholesterolemic effects of curcumin via up-regulation of cholesterol 7a-hydroxylase in rats fed a high fat diet. Nutr Res Pract 4, 191-195.
97. Tu Y, Sun D, Zeng X, et al. (2014) Piperine potentiates the hypocholesterolemic effect of curcumin in rats fed on a high fat diet. Exp Ther Med 8, 260-266.
98. Zambón D, Quintana M, Mata P, et al. (2010) Higher incidence of mild cognitive impairment in familial hypercholesterolemia. Am J Med 123, 267-274.
99. Refolo LM, Pappola MA, Malester B, et al. (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 7, 690-691.
100. Xiao Z, Zhang A, Lin J, et al. (2014) Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in Abeta insult in vitro. PLOS ONE 9, e101251.
101. Lim GP, Chu T, Yang F, et al. (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21, 8370-8377.
102. Wang YJ, Thomas P, Zhong JH, et al. (2009) Consumption of grape seed extract prevents amyloid-deposition and attenuates inflammation in brain of an Alzheimer's disease mouse. Neurotox Res 15, 3-14.
103. Ma QL, Yang F, Rosario ER, et al. (2009) 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 29, 9078-9089.
104. Frautschy SA, Hu W, Kim P, et al. (2001) Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 22, 993-1005.
105. Fenech M, Thomas P (2010) Grape seed polyphenols and curcumin reduce genomic instability events in a transgenic mouse model for Alzheimer's disease. Alzheimers Dement 6, S70-S72.
106. Belviranli M, Okudan N, Atalik K, et al. (2013) Curcumin improves spatial memeory and decreases oxidative damage in aged female rats. Biogerontology 14, 187-196.
107. Ahmed T, Enam SA, Gilani AH (2010) Curcuminoids enhance memory in an amyloid-infused rat model of Alzheimer's disease. Neuroscience 169, 1296-1306.
108. Kim SJ, Son TG, Park HR, et al. (2008) Curcumin stimulates proliferation of embryonic neural progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 283, 14497-14505.
109. Gerenu G, Liu K, Chojnacki JE, et al. (2015) Curcumin/melatonin hybrid 5-(4-hydroxy-phenyl)-3-oxo-pentanoic acid [2-(5-methoxy-1H-indol-3-yl)-ethyl]-amide ameliorates ADlike pathology in the APP/PS1 mouse model. ACS Chem Neurosci 6, 1393-1399.
110. Yanagisawa D, Ibrahim NF, Taguchi H, et al. (2015) Curcumin derivative with the substitution at C-4 position, but not curcumin, is effective against amyloid pathology in APP/PS1 mice. Neurobiol Aging 36, 201-210.
111. Dong S, Zeng Q, Mitchell ES, et al. (2012) Curcumin enhances neurogenesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PLOS ONE 7, e31211.
112. Ghoneim AI, Abdel-Naim AB, Khalifa AE, et al. (2002) Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. Pharmacol Res 46, 273-279.
113. Thiyagarajan M, Sharma SS (2004) Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Life Sci 74, 969-985.
114. Jiang J, Wang W, Sun YJ, et al. (2007) Neuroprotective effect of curcumin on focal cerebral ischemic rats by preventing blood-brain barrier damage. Eur J Pharmacol 561, 54-62.
115. Wang YF, Gu YT, Qin GH, et al. (2013) Curcumin ameliorates the permeability of the blood-brain barrier during hypoxia by upregulating heme oxygenase-1 expression in brain microvascular endothelial cells. J Mol Neurosci 51, 344-351.
116. Tsai YM, Chien CF, Lin LC, et al. (2011) Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int J Pharm 416, 331-338.
117. Cheng KK, Yeung CF, Ho SW, et al. (2013) Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice. AAPS J 15, 324-336.
118. Anand P, Nair HB, Sung B, et al. (2010) Design of curcumin loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo. Biochem Pharmacol 79, 330-338.
119. Zona C, La Ferla B (2011) Synthesis of labeled curcumin derivatives as tools for in vitro blood brain barrier trafficking studies. J Label Compd Radiopharm 54, 629-632.
120. Re F, Gregori M, Masserini M (2012) Nanotechnology for neurodegenerative disorders. Nanomed Nanotechnol 8, S51-S58.
121. Shahani K, Swaminathan SK, Freeman D, et al. (2010) Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention. Cancer Res 70, 4443-4452.
122. Chiu SS, Lui E, Majeed M, et al. (2011) Differential distribution of intravenous curcumin formulations in the rat brain. Anticancer Res 31, 907-911.
123. Shaikh J, Ankola DD, Beniwal V, et al. (2009) Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci 37, 223-230.
124. Ahmed T, Gilani AH (2009) Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease. Pharmocol Biochem Behav 91, 554-559.
125. Gauthier S, Molinuevo JL (2013) Benefits of combined cholinesterase inhibitor and memantine treatment in moderate-severe AD. Alzheimers Dement 9, 326-331.
126. Peeyush KT, Antony S, Sonan S, et al. (2011) Role of curcumin in the prevention of cholinergic mediated cortical dysfunctions in streptozotocin-induced diabetic rats. Mol Cell Endocrinol 331, 1-10.
127. Rajasekar N, Dwivedi S, Tota SK, et al. (2013) Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice. Eur J Pharmacol 715, 381-394.
128. Tiwari V, Chopra K (2013) Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain. Neuroscience 6, 147-158.
129. Orhan IE (2013) Nature: a substantial source of auspicious substances with acetylcholinesterase inhibitory action. Curr Neuropharmacol 11, 379-387.
130. Bulteau AL, Moreau M, Saunois A, et al. (2006) Algae extractmediated stimulation and protection of proteasome activity within human keratinocytes exposed to UVA and UVB irradiation. Antioxid Redox Signal 8, 136-143.
131. Cole GM, Teter B, Frautschy SA (2007) Neuroprotective effects of curcumin. Adv Exp Med Biol 595, 197-212.
132. Ikonomovic MD, Abrahamson EE, Uz T, et al. (2008) Increased 5-lopoxygenase immunoreactivity in the hippocampus of patients with Alzheimer's disease. J Histochem Cytochem 56, 1065-1073.
133. Qu J, Uz T, Manev H (2000) Inflammatory 5-LOX mRNA and protein are increased in brain of aging rats. Neurobiol Aging 21, 647-652.
134. Firuzi O, Zhuo J, Chinnici CM, et al. (2008) 5-Lipoxygenase gene disruption reduces amyloid-pathology in a mouse model of Alzheimer's disease. FASEB J 22, 1169-1178.
135. Ohno M (2014) Roles of eIF2 kinases in the pathogenesis of Alzheimer's disease. Front Mol Neurosci 7, 1-8.
136. Valera E, Dargusch R, Maher PA, et al. (2013) Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer's disease. J Neurosci 33, 10512-11052.
137. Baum L, Lam C, Cheung S, et al. (2008) Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharm 28, 110-114.
138. Ringman JM, Frautschy SA, Cole GM, et al. (2005) A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer Res 2, 131-136.
139. Commandeur J, Vermeulen N (1996) Cytotoxicity and cytoprotective activities of natural compounds. The case of curcumin. Xenobiotica 26, 667-680.
140. Ganguli M, Chandra V, Kamboh MI, et al. (2000) Apolipoprotein E polymorphism and Alzheimer disease: the Indo-US cross-national dementia study. Arch Neurol 57, 824-830.
141. Chandra V, Pandav R, Dodge H, et al. (2001) Incidence of Alzheimer's disease in a rural community in India The Indo-US study. Neurology 57, 985-989.
142. Shaji S, Bose S, Verghese A (2005) Prevalence of dementia in an urban population in Kerala, India. B J Psychiatry 186, 136-140.
143. Ng TP, Chiam PC, Lee T, et al. (2006) Curry consumption and cognitive function in the elderly. Am J Epidemiol 164, 898-906.
144. Cox KH, Pipingas A, Scholey AB (2015) Investigation of the effects of solid lipid curcumin on cognition and mood in a healthy older population. J Psychopharmacol 29, 642-651.
145. Ringman JM, Frautschy SA, Teng E, et al. (2012) Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebocontrolled study. Alzheimer's Res Ther 4, 43-51.
146. DiSilvestro RA, Joseph E, Zhao S, et al. (2012) Diverse effects of a low dose supplement of lipidated curcumin in healthy middle aged people. Nutr J 11, 79-87.
147. van Stegerena A, Rohlederb N, Everaerda W, et al. (2006) Salivary alpha amylase as marker for adrenergic activity during stress: effect of betablockade. Psychoneuroendocrinology 31, 137-141.
148. Gallacher DV, Petersen OH (1983) Stimulus-secretion coupling in mamalian salivary glands. Intern Rev Physiol 28, 1-52.
149. Chatterton RT, Vogelsong KM, Lu YC, et al. (1996) Salivary alpha-amylase as a measure of endogenous adrenergic activity. Clin Physiol 16, 433-448.
150. Hishikawa N, Takahashi Y, Amakusa Y, et al. (2012) Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia. Ayu 33, 499-504.
151. Mastroeni D, Grover A, Delvaux E, et al. (2011) Epigenetic mechanisms in Alzheimer's disease. J Neurobiol Aging 32, 1161-1180.
152. Daniilidou M, Koutroumani M, Tsolaki M (2011) Epigenetic mechanisms in Alzheimer's disease. Curr Med Chem 18, 1751-1756.
153. Balazs R, Vernon J, Hardy J (2011) Epigenetic mechanisms in Alzheimer's disease:progress but much to do. Neurobiol Aging 32, 1181-1187.
154. Chouliaras L, Rutten BPF, Kenis G, et al. (2010) Epigenetic regulation in the pathophysiology of Alzheimer's disease. Prog Neurobiol 90, 498-510.
155. Teiten MH, Dicato M, Diederich M (2013) Curcumin as a regulator of epigenetic events. Mol Nutr Food Res 57, 1619-1629.
156. Reuter S, Gupta SC, Park B, et al. (2011) Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr 6, 93-108.
157. Du L, Xie Z, Wu LC, et al. (2012) Reactivation of RASSF1A in breast cancer cells by curcumin. Nutr Cancer 64, 1228-1235.
158. Sezgin Z, Dincer Y (2014) Alzheimer's disease and epigenetic diet. Neurochem Int 78, 105-116.
159. Li YJ, Xu M, Gao ZH, et al. (2013) Alterations of serum levels of BDNF-related miRNAs in patients with depression. PLOS ONE 8, e63648.
160. Lopresti AL, Maes M, Marker GL, et al. (2014) Curcumin for the treatment of major depression: a randomised, double-blind, placebo controlled study. J Affect Disord 167, 368-375.
161. Davinelli S, Calabrese V, Zella D, et al. (2014) Epigenetic nutraceutical diets in Alzheimer's disease. J Nutr Health Aging 18, 800-805.
162. Ansari R, Mahta A, Mallack E, et al. (2014) Hyperhomocysteinemia and neurologic disorders: a review. J Clin Neurol 10, 281-288.
163. Mattson MP, Shea TB (2003) Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26, 137-146.
164. Fux R, Kloor D, Hermes M, et al. (2005) Effect of acute hyperhomocysteinemia on methylation potential of erthrocytes and on DNA methylation of lymphocytes in healthy male volunteers. Am J Renal Physiol 289, F786-F792.
165. Ataie A, Sabetkasaei M, Haghparast A, et al. (2010) Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impariement and oxidative stress in rat brain. J Med Food 13, 821-826.
166. Cheng AL, Hsu CH, Lin CH, et al. (2001) Phase I clinical trial of curcumin, a chemopreventative agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21, 2895-2900.
167. Gupta SC, Kismali G, Aggarwal BB (2013) Curcumin, a component of turmeric: from farm to pharmacy. Biofactors 39, 2-13.
168. Pan CJ, Tang JJ, Weng YJ, et al. (2006) Preparation, characterization and anticoagulation of curcumin-eluting controlled biodgradable coating stents. J Control Release 116, 2-49.
169. Dong-Chan K, Sae-Kwang K, Jong-Sup B (2012) Anticoagulant activities of curcumin and its derivative. BMB Rep 45, 221-226.
170. Belkacemi A, Doggui S, Dao L, et al. (2011) Challenges associated with curcumin therapy in Alzheimer disease. Exp Rev Mol Med 13, e34.
171. Sharma RA, Steward WP, Gescher AJ (2007) The molecular targets and therapeutic uses of curcumin in health and disease. Adv Exp Med Biol 595, 453-470.
172. Ireson C, Orr S, Jones DJL (2001) Characterization of metabolites of the chemopreventative agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prosaglandin E2 production. Cancer Res 61, 1058-1064.
173. Benny M, Anthony B (2006) Bioavailability of Biocurcumax™(BCM-95™). Research and Development Laboratory, Arjuna Natural Extracts Ltd, Binanipuram.
174. Pescosolido N, Giannotti R, Plateroti AM, et al. (2014) Curcumin: therapeutical potential in ophthalmology. Planta Med 80, 249-254.
175. Rachmawati H, Budiputra DK, Mauludin R (2014) Curcumin nanoemulsion for transdermal application: formulation and evaluation. Drug Dev Ind Pharm 41, 560-566.
176. McClure R, Yanagisawa D, Stec D, et al. (2015) Inhalable curcumin: offering the potential for translation to imaging and treatment of Alzheimer's disease. J Alzheimers Dis 44, 283-295.
177. Antony B, Merina B, Iyer VS, et al. (2008) A pilot cross-over study to evaluate human oral bioavailability of BCM-95CG (Biocurcumax), a novel bioenhanced preparation of curcumin. Indian J Pharm Sci 70, 445-449.
178. Merina B, Antony B (2006) Bioavailability of Biocurcumax (BCM-095). Spice India 2, 11-16.
179. Jayaraj RL, Elangovan N, Dhanalakshmi C, et al. (2014) CNB-001, a novel pyrazole derivative mitigates motor impairments associated with neurodegeneration via suppression of neuroinflammatory and apoptotic response in experimental Parkinson's disease mice. Chem Biol Interact 220, 149-157.
180. Maher P, Akaishi T, Schubert D, et al. (2010) A pyrazole derivative of curcumin enhances memory. Neurobiol Aging 31, 706-709.
181. Liu Y, Dargusch R, Maher P, et al. (2008) A broadly neuroprotective derivative of curcumin. J Neurochem 105, 1336-1345.
182. Prasad S, Tyagi AK, Aggarwal BB (2014) Recent developments in delivery, bioavailability, absorption and metabolism of curcumin: the golden pigment from golden spice. Cancer Res Treat 46, 2-18.
183. Stockert JC, Del Castillo P, Gomez A, et al. (1989) Fluorescence reaction of chromatin by curcumin.Z NaturforschC44, 327-329.
184. Wang F, Wu X, Wang F, et al. (2006) The sensitive fluorimetric method for the determination of curcumin using the enhancement of mixed micelle. J Fluoresc 16, 53-59.
185. Ryu EK, Choe YS, Lee KH, et al. (2006) Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for-amyloid plaque imaging. J Med Chem 49, 6111-6119.
186. Mohorko N, Repovš G, Popovic M, et al. (2010) Curcumin labeling of neuronal fibrillar tau inclusions in human brain samples. J Neuropathol Exp Neurol 69, 405-414.
187. Koronyo-Hamaoui M, Koronyo Y, Ljubimov AV, et al. (2011) Identification of amyloid plaques in retinas from Alzheimer's patients and noninvasive in vivo optical imaging of retinal plaques in a mouse model. Neuroimage, S204-S217.
188. Kayabasi U, Sergott RC, Rispoli M (2014) Retinal examination for the diagnosis of Alzheimer's disease. Int J Ophthalmol Clin Res 1, 1-4.
189. Cheng KK, Chan PS, Fan S, et al. (2015) Curcumin-conjugated magnetic nanoparticles for detecting amyloid plaques in Alzheimer's disease mice using magnetic resonance imaging (MRI). Biomaterials 44, 155-172.
190. Patil R, Gangalum PR, Wagner S, et al. (2015) Curcumin targeted, polymalic acid-based MRI contrast agent for the detection of abeta plaques in Alzheimer's disease. Macromol Biosci 15, 1212-1217.
191. Frost S, Martins RN, Kanagasingam Y (2010) Ocular biomarkers for early detection of Alzheimer's disease. J Alzheimers Dis 22, 1-16.