Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in alzheimer disease: Therapeutic implications

Rejuvenation Research

Volumn 13, Issue 2-3, 2010, Pages 301-313

  Candore, Giuseppina ^a   Bulati, Matteo ^a   Caruso, Calogero ^a   Castiglia, Laura ^a   Colonna Romano, Giuseppina ^a   Di Bona, Danilo ^a   Duro, Giovanni ^b   Lio, Domenico ^a   Matranga, Domenica ^a   Pellicanò, Mariavaleria ^a   Rizzo, Claudia ^a   Scapagnini, Giovanni ^c   Vasto, Sonya ^a  

^a UNIVERSITY OF PALERMO   (Italy)

^b CNR Consiglio Nazionale delle Ricerche   (Italy)

^c UNIVERSITY OF MOLISE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN E; CAFFEIC ACID PHENETHYL ESTER; CARNOSOL; CENTRAL NERVOUS SYSTEM AGENTS; CHOLESTEROL; CURCUMIN; CYTOKINE; CYTOKINE RECEPTOR ANTAGONIST; EPIGALLOCATECHIN GALLATE; ETHYL FERULATE; NONSTEROID ANTIINFLAMMATORY AGENT; RESVERATROL; ROSEOLIC ACID; SULFORAPHANE; UNCLASSIFIED DRUG; ZERUMBONE;

ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; DIET; DISEASE ASSOCIATION; HUMAN; IMMUNE RESPONSE; IMMUNOTHERAPY; INFLAMMATION; NEUROPROTECTION; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 77950212895     PISSN: 15491684     EISSN: None     Source Type: Journal    
DOI: 10.1089/rej.2009.0993     Document Type: Review

References (149)

1. Hebert LE, Scherr PA, Beckett LA, Albert MS, Pilgrim DM, Chown MJ, Funkenstein HH, Evans DA. Age-specific incidence of Alzheimer's disease in a community population. JAMA. 1995;273:1354-1359.
2. Wang XP, Ding HL. Alzheimer's disease: Epidemiology, genetics, and beyond. Neurosci Bull 2008;24:105-109.
3. Steinman L. Nuanced roles of cytokines in three major human brain disorders. J Clin Invest. 2008;118:3557-3563.
4. Vasto S, Candore G, List̀ F, Balistreri CR, Colonna-Romano G, Malavolta M, Lio D, Nuzzo D, Mocchegiani E, Di Bona D, Caruso C. Inflammation, genes and zinc in Alzheimer's disease. Brain Res Rev 2008;58:96-105.
5. Vasto S, Candore G, Duro G, Lio D, Grimaldi MP, Caruso C. Alzheimer's disease and genetics of inflammation: a pharmacogenomic vision. Pharmacogenomics 2007; 8:1735-1745.
6. Eikelenboom P, Veerhuis R, Scheper W, Rozemuller AJ, van Gool WA, Hoozemans JJ. The significance of neuroin-flammation in understanding Alzheimer's disease. J Neural Transm 2006;113:1685-1695.
7. Gasparini L, Racchi M, Binetti G, Trabucchi M, Solerte SB, Alkon D, Etcheberrigaray R, Gibson G, Blass J, Paoletti R, Govoni S. Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease. FASEB J 1998;12:17-34.
8. Racchi M, Uberti D, Govoni S, Memo M, Lanni C, Vasto S, Candore G, Caruso C, Romeo L, Scapagnini G. Alzheimer's disease: New diagnostic and therapeutic tools. Immun Ageing 2008;5:7.
9. McNaull BB, Todd S, McGuinness B, Passmore AP. Inflammation and anti-inflammatory strategies for Alzheimer's disease. Gerontology 2010;56:3-14.
10. Scapagnini G, Caruso C, Vasto S, Pascale A, Romeo L, D'Agata V. Genetic risk factors and candidate biomarkers for Alzheimer's disease. Front Biosci 2010;1:616-622.
11. Britschgi M, Wyss-Coray T. Systemic and acquired immune responses in Alzheimer's disease. Int Rev Neurobiol. 2007;82:205-233.
12. McGeer EG, McGeer PL. The importance of inflammatory mechanisms in Alzheimer disease. Exp Geront 1998;33: 371-378.
13. Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi G, Caruso C Innate immunity and inflammation in ageing: A key for understanding age-related diseases. Immun Ageing 2005;2:8.
14. Wilson J T. Head injury and Alzheimer's disease. J Neurol Neurosurg Psychiatry 2003;74:857-862.
15. Smith J.D. Apolipoproteins and aging: Emerging mechanisms. Ageing Res. Rev 2002;1:345-365.
16. Sheng JG, Bora SH, Xu G, Borchelt DR, Price DL, Koliatsos VE. Lipopolysaccharide-induced-neuroinflammation increases intracellular accumulation of amyloid precursor protein and amyloid beta peptide in APPswe transgenic mice. Neuro-biol Dis 2003;14:133-145.
17. Perry VH, Cunningham C, Holmes C. Systemic infections and inflammation affect chronic neurodegeneration. Nat Rev Immunol 2007;7:161-167.
18. Holmes C, El-Okl M, Williams A, Cunningham C, Wil-cockson D and Perry V. Systemic infection, interleukin 1b, and cognitive decline in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2003;74:788-789.
19. Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 1999;4:1-6.
20. Kuo LC, Polson AM, Kang T. Associations between peri-odontal diseases and systemic diseases: A review of the inter-relationships and interactions with diabetes, respiratory diseases, cardiovascular diseases and osteoporosis. Public Health 2008;122:417-433.
21. Campisi G, Chiappelli M, De Martinis M, Franco V, Ginaldi L, Guiglia R, Licastro F, Lio D. Pathophysiology of age-related diseases. Immun Ageing 2009;6:12.
22. Seymour GJ, Ford PJ, Cullinan MP, Leishman S, Yamazaki K. Relationship between periodontal infections and systemic disease. Clin Microbiol Infect 2007;13(Suppl 4): 3-10.
23. Riviere GR, Riviere KH, Smith KS. Molecular and immu-nological evidence of oral Treponema in the human brain and their association with Alzheimer's disease. Oral Mi-crobiol Immunol 2002;17:113-118.
24. Romeo HE, Tio DL, Rahman SU, Chiappelli F, Taylor AN. The glossopharyngeal nerve as a novel pathway in im-mune-to-brain communication: Relevance to neuroimmune surveillance of the oral cavity. J Neuroimmunol 2001;115: 91-100.
25. Chalmers JM, Carter KD, Spencer AJ. Oral diseases and conditions in community-living older adults with and without dementia. Spec Care Dentist 2003;23:7-17.
26. Riley KP, Snowdon DA, Markesbery WR. Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study. Ann Neurol 2002; 51:567-577.
27. Stein PS, Desrosiers M, Donegan SJ, Yepes JF, Kryscio RJ. Tooth loss, dementia and neuropathology in the Nun Study. J Am Dent Assoc 2007;138:1314-1322.
28. in t' Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen T, Breteler MM, Stricker BH. Non-steroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med. 2001;345:1515-1521.
29. McGeer PL, Schulzer M, McGeer EG, Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: A review of 17 epidemiologic studies. Neurology 1996;47:425-432.
30. Breitner JC. NSAIDs and Alzheimer's disease: How far to generalise from trials? Lancet Neurol 2003;2:527.
31. Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer's disease: Systematic review and meta-analysis of observational studies. BMJ 2003;327:128-133.
32. ADAPT Research Group, Martin BK, Szekely C, Brandt J, Piantadosi S, Breitner JC, Craft S, Evans D, Green R, Mullan M. Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): Results of a randomized, controlled trial of naproxen and celecoxib. Arch Neurol 2008;65:896-905.
33. Bregman N, Karni A, Korczyn AD. Can treatment with nonsteroidal anti-inflammatory drugs protect from dementia? Arch Neurol 2009;66:539-540.
34. Vlad SC, Miller DR, Kowall NW, Felson DT. Protective effects of NSAIDs on the development of Alzheimer disease. Neurology 2008;70:1672-1677.
35. Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O'Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T. Inflammation and Alzheimer's disease. Neurobiol Aging 2000; 21:383-421.
36. Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, White CL 3rd, Araoz C.Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc Natl Acad Sci USA 1989; 86: 7611-7615.
37. Di Bona D, Plaia A, Vasto S, Cavallone L, Lescai F, Fran-ceschi C, Licastro F, Colonna-Romano G, Lio D, Candore G, Caruso C. Association between the interleukin-1beta polymorphisms and Alzheimer's disease: A systematic review and meta-analysis. Brain Res Rev 2008;59:155-163.
38. Di Bona D, Candore G, Franceschi C, Licastro F, Colonna-Romano G, Cammà C, Lio D, Caruso C. Systematic review by meta-analyses on the possible role of TNF-alpha polymorphisms in association with Alzheimer's disease. Brain Res Rev 2009;61:60-68.
39. Wyss-Coray T, Lin C, Yan F, Yu GQ, Rohde M, McConlo-gue L, Masliah E, Mucke L. TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat Med 2001;7:612-618.
40. Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, Carter ND, Spector TD. Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 1999;8:93-97.
41. Luedecking EK, DeKosky ST, Mehdi H, Ganguli M, Kamboh MI. Analysis of genetic polymorphisms in the transforming growth factor-beta1 gene and the risk of Alzheimer's disease. Hum Genet 2000;106:565-569.
42. Araria-Goumidi L, Lambert JC, Mann DM, Lendon C, Frigard B, Iwatsubo T, Cottel D, Amouyel P, Chartier-Harlin MC. Association study of three polymorphisms of TGF-beta1 gene with Alzheimer's Disease. J Neurol Neu-rosurg Psychiatry 2002;73:62-64.
43. Arosio B, Bergamaschini L, Galimberti L, La Porta C, Zanetti M, Calabresi C, Scarpini E, Annoni G, Vergani C.\+10 T=C polymorphisms in the gene of transforming growth factor-beta1 are associated with neurodegenera-tion and its clinical evolution. Mech Ageing Dev 2007;128: 553-557.
44. van Oijen M, Arp PP, de Jong FJ, Hofman A, Koudstaal PJ, Uitterlinden AG, Breteler MM. Polymorphisms in the in-terleukin 6 and transforming growth factor beta1 gene and risk of dementia. The Rotterdam Study. Neurosci Lett 2006;402:113-117.
45. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34:939-944.
46. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clin Trials 1986;7:177-188.
47. Nishimura M, Sakamoto T, Kaji R, Kawakami H. Influence of polymorphisms in the genes for cytokines and glutathi-one S-transferase omega on sporadic Alzheimer's disease. Neurosci Lett 2004;368:140-143.
48. Dickson MR, Perry RT, Wiener H, Go RC. Association studies of transforming growth factor-beta 1 and Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet 2005;139B:38-41.
49. Rodr?́guez-Rodŕ?guez E, Sánchez-Juan P, Mateo I, Llorca J, Infante J, Garc?́a-Gorostiaga I, Berciano J, Combarros O. Serum levels and genetic variation of TGF-beta1 are not associated with Alzheimer's disease. Acta Neurol Scand 2007;116:409-412.
50. Hamaguchi T, Okino S, Sodeyama N, Itoh Y, Takahashi A, Otomo E, Matsushita M, Mizusawa H, Yamada M. Association of a polymorphism of the transforming growth fac-tor-beta1 gene with cerebral amyloid angiopathy. J Neurol Neurosurg Psychiatry 2005; 76:696-699.
51. Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP Listi F, Nuzzo D, Lio D, Caruso C. Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 2007;128:83-91.
52. Licastro F, Porcellini E, Caruso C, Lio D, Corder EH. Genetic risk profiles for Alzheimer's disease: Integration of APOE genotype and variants that up-regulate inflammation. Neurobiol Aging 2007;28:1637-1643.
53. Perry VH, The influence of systemic inflammation on inflammation in the brain: implications for chronic neuro-degenerative disease. Brain Behav Immun 2004;18:407-413.
54. Tobinick E. Perispinal etanercept for treatment of Alzheimer's disease. Curr Alzheimer Res 2007;4:550-552.
55. Tobinick E. Perispinal etanercept for neuroinflammatory disorders. Drug Discov Today 2009;14:168-177.
56. Tobinick E. Tumour necrosis factor modulation for treatment of Alzheimer's disease: rationale and current evidence. CNS Drugs 2009;23:713-725.
57. Reale M, Iarlori C, Gambi F, Lucci I, Salvatore M, Gambi D. Acetylcholinesterase inhibitors effects on oncostatin-M, in-terleukin-1 beta and interleukin-6 release from lymphocytes of Alzheimer's disease patients. Exp Gerontol 2005;40: 165-171.
58. Larbi A, Pawelec G, Witkowski JM, Schipper HM, Derho-vanessian E, Goldeck D, Fulop T. Dramatic shifts in circulating CD4 but not CD8 T cell subsets in mild Alzheimer's disease. J Alzheimers Dis 2009;17: 91-103.
59. Licastro F, Caruso C. Is immunotherapy an effective treatment for Alzheimer's disease? Immun Ageing 2004;1:3.
60. Weksler ME. The immunotherapy of Alzheimer's disease. Immun Ageing 2004;1:2
61. Relkin NR, Szabo P, Adamiak B, Burgut T, Monthe C, Lent RW, Younkin S, Younkin L, Schiff R, Weksler ME. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol Aging 2009;30: 1728-1736.
62. Fillit H, Hess G, Hill J, Bonnet P, Toso C. IV immuno-globulin is associated with a reduced risk of Alzheimer disease and related disorders. Neurology 2009;73:180-185.
63. Szabo P, Relkin N, Weksler ME. Natural human antibodies to amyloid beta peptide. Autoimmun Rev 2008;7: 415-420.
64. Negi VS, Elluru S, Siberil S, Graff-Dubois S, Mouthon L, Kazatchkine MD, Lacroix-Desmazes S, Bayry J, Kaveri SV. Intravenous immunoglobulin: An update on the clinical use and mechanisms of action. J Clin Immunol 2007;27: 233-245.
65. Nussbaum RL and Ellis, CE. Genomic medicine: Alzheimer's disease and Parkinson's disease. N Engl J Med 2003;348:1356-1364.
66. Bird, TD, Genetic factors in Alzheimer's disease. N Engl J Med 2005;352:862-864.
67. Cordy M, Hooper NM, Turner AJ. The involvement of lipid rafts in Alzheimer's disease. Mol Membr Biol 2006;23: 111-122.
68. Finch CE, Morgan TE. Systemic inflammation, infection, ApoE alleles, and Alzheimer's disease: A position paper. Curr Alzheimer Res 2007;4:185-189.
69. Kim J, Basak JM, Holtzman DM. The role of apolipoprotein E in Alzheimer's disease. Neuron 2009;63:287-303.
70. Kivipelto M, Solomon A. Cholesterol as a risk factor for Alzheimer's disease\epidemiological evidence. Acta Neurol Scand 2006;114:50-57.
71. de Chaves EP, Narayanaswami V. Apolipoprotein E and cholesterol in aging and disease in the brain. Future Lipidol 2008;3:505-530.
72. Kandiah N, Feldman HH. Therapeutic potential of statins in Alzheimer's disease. J Neurol Sci 2009;283:230-234.
73. McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev 2009;15:CD003160.
74. Moreiras O, van Staveren WA, Amorim Cruz JA, Carbajal A, de Henauw S, Grunenberger F, Roszkowski W. Longitudinal changes in the intake of energy and macronutrients of elderly Europeans. SENECA Investigators. Eur J Clin Nutr 1996;50;S67-S76. (Pubitemid 26283327)
75. Breteler MM, Claus JJ, Grobbee DE, Hofman A. Cardiovascular disease and distribution of cognitive function in elderly people: The Rotterdam Study. BMJ 1994;308:1604.
76. Naor M, Steingrüber HJ, Westhoff K, Schottenfeld-Naor Y, Gries AF. Cognitive function in elderly non-insulin-dependent diabetic patients before and after inpatient treatment for metabolic control. J Diabetes Complications 1997;11:40-46.
77. Guo Z, Fratiglioni L, Winblad B, Viitanen M. Blood pressure and performance on the Mini-Mental State Examination in the very old. Cross-sectional and longitudinal data from the Kungsholmen Project. Am J Epidemiol 1997; 145:1106-1113.
78. Frisoni GB, Fratiglioni L, Fastbom J, Guo Z, Viitanen M, Winblad B. Mild cognitive impairment in the population and physical health: Data on 1,435 individuals aged 75 to 95. J Gerontol A Biol Sci Med Sci 2000;55:M322-M328.
79. Luchsinger JA, Tang MX, Shea S, Mayeux R. Caloric intake and the risk of Alzheimer disease. Arch Neurol 2002;59:1258-1263.
80. Engelhart MJ, Geerlings MI, Ruitenberg A, Van Swieten JC, Hofman A, Witteman JC, Breteler MM. Diet and risk of dementia: Does fat matter?: The Rotterdam Study. Neurology 2002;59:1915-1921.
81. Solfrizzi V, Colacicco AM, D'Introno A, Capurso C, Del Parigi A, Capurso SA, Argentieri G, Capurso A, Panza F. Dietary fatty acids intakes and rate of mild cognitive impairment. The Italian Longitudinal Study on Aging. Exp Gerontol 2006;41:619-627.
82. Solfrizzi V, Colacicco AM, D'Introno A, Capurso C, Torres F, Rizzo C, Capurso A, Panza Dietary intake of unsaturated fatty acids and age-related cognitive decline: A 8.5-year follow-up of the Italian Longitudinal Study on Aging. Neurobiol Aging 2006;27:1694-1704.
83. Del Parigi A, Panza F, Capurso C, Solfrizzi V. Nutritional factors, cognitive decline, and dementia. Brain Res Bull 2006;69:1-19. (Pubitemid 43185339)
84. Orsitto G, Seripa D, Panza F, Franceschi M, Cascavilla L, Placentino G, Paris F, Solfrizzi V, Dallapiccola B, Pilotto AJ. Apolipoprotein E genotypes in mild cognitive impairment subtypes. Am Geriatr Soc 2006;54:1965-1966.
85. Wengreen HJ, Munger RG, Corcoran CD, Zandi P, Hayden KM, Fotuhi M, Skoog I, Norton MC, Tschanz J, Breitner JC, Welsh-Bohmer KA. Antioxidant intake and cognitive function of elderly men and women: the Cache County Study. J Nutr Health Aging. 2007;11:230-237.
86. Morris MC, Evans DA, Schneider JA, Tangney CC, Bienias JL, Aggarwal NT. Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease. J Alz-heimers Dis 2006;9:435-443.
87. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Associations of vegetable and fruit consumption with age-related cognitive change. Neurology 2006;67:1370-1376.
88. Shukitt-Hale B, Cheng V, Joseph JA. Effects of blackberries on motor and cognitive function in aged rats. Nutr Neu-rosci 2009;12:135-140.
89. Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. Mediterranean diet and mild cognitive impairment. Arch Neurol 2009;66:216-225.
90. Ross GW, Petrovitch H, White LR, Masaki KH, Li CY, Curb JD, Yano K, Rodriguez BL, Foley DJ, Blanchette PL, Havlik R. Characterization of risk factors for vascular dementia: the Honolulu-Asia Aging Study. Neurology 1999;53: 337-343.
91. Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med 1997;23:134-147.
92. Butterfield DA, Stadtman ER. Protein oxidation processes in aging brain. Adv Cell Aging Gerontol 1997;2:161-191.
93. Halliwell B. Biochemistry of oxidative stress. Biochem Soc Trans 2007;35:1147-1150.
94. de la Monte SM, Wands JR. Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease. J Alzheimers Dis 2006;9:167-181.
95. Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer's disease brain: Central role for amyloid beta-peptide. Trends Mol Med 2001;7: 548-554.
96. Clementi ME, Pezzotti M, Orsini F, Sampaolese B, Mezzo-gori D, Grassi C, Giardina B, Misiti F.Alzheimer's amyloid beta peptide (1-42) induces cell death in human neuro-blastoma via bax=bcl-2 ratio increase: an intriguing role for methionine 35. Biochem Biophys Res Commun 2006;342: 206-213.
97. ButterWeld DA, Boyd-Kimball D. The critical role of me-thionine 35 in Alzheimer's amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity. Biochim Biophys Acta 2005;1703:149-156.
98. Wilkinson BL, Landreth GE. The microglial NADPH oxi-dase complex as a source of oxidative stress in Alzheimer's disease. J Neuroinflammation 2006;9;3:30.
99. Park L, Anrather J, Zhou P, Frys K, Pitstick R, Younkin S, Carlson GA, Iadecola C. NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid beta peptide. J Neurosci 2005;25: 1769-1777.
100. Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA. Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: The role of vitagenes. In Vivo 2004;18:245-267.
101. Calabrese V, Sultana R, Scapagnini G, Guagliano E, Sa-pienza M, Bella R. Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease. Antioxid Redox Signal 2006;8;1975-1986.
102. Finkel T, Holbrook NJ.Oxidants, oxidative stress and the biology of aging. Nature 2000;408:239-247.
103. Hensley K, Hall N, Subramaniam R, Cole P, Harris M, Aksenov M, Aksenova M, Gabbita SP, Wu JF, Carney JM. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem 1995;65:2146-2156.
104. Sultana R, Boyd-Kimball D, Poon HF, Cai J, Pierce WM, Klein JB, Merchant M, Markesbery WR, ButterWeld DA. Redox proteomics identiWcation of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: An approach to understand pathological and biochemical alterations in AD. Neurobiol Aging 2006;27: 1564-1576.
105. Scapagnini G, D'Agata V, Calabrese V, Pascale A, Colom-brita C, Alkon DL, Cavallaro S.Gene expression profiles of heme oxygenase isoforms in the rat brain. Brain Res 2002;954:31-39.
106. Calabrese V, Signorile A, Cornelius C, Mancuso C, Sca-pagnini G, Ventimiglia B, Ragusa N, Dinkova-Kostova A. Practical approaches to investigate redox regulation of heat shock protein expression and intracellular glutathione redox state. Methods Enzymol 2008;441:83-110.
107. Premkumar DR, Smith MA, Richey PL, Petersen RB, Cas-tellani R, Kutty RK. Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer's disease. J Neurochem 1996;65:1399-1402.
108. Takeda A, Perry G, Abraham NG, Dwyer BE, Kutty RK, Laitinen JT, Petersen RB, Smith MA. Overexpression of heme oxygenase in neuronal cells, the possible interaction with Tau. J Biol Chem 2000;275:5395-5399.
109. Mateo I, Sánchez-Juan P, Rodŕ?guez-Rodr?́guez E, Infante J, Vázquez-Higuera JL, Garć?a-Gorostiaga I, Berciano J, Combarros O. Synergistic effect of heme oxygenase-1 and tau genetic variants on Alzheimer's disease risk. Dement Geriatr Cogn Disord 2008;26:339.
110. Takahashi M, Dore S, Ferris C.D, Tomita T, Sawa A, Wo-losker H, Borchelt DR, Iwatsubo TS, Kim H, Thinakaran G, Sisodia SS, Snyder SH. Amyloid precursor proteins inhibit heme oxygenase activity and augment neurotoxicity in Alzheimer's disease. Neuron 2002;28:461-473.
111. Schipper HM. Heme oxygenase-1: Role in brain aging and neurodegeneration. Exp Gerontol 2000;35:821-830.
112. Colombrita C, Calabrese V, Stella AM, Mattei F, Alkon DL, Scapagnini G. Regional rat brain distribution of heme oxygenase-1 and manganese superoxide dismutase mRNA: Relevance of redox homeostasis in the aging processes. Exp Biol Med 2003;228:517-524.
113. Chen K, Gunter K, Maines MD. Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death. J Neurochem 2000;75:304-312.
114. Le WD, Xie, WJ, Appel SH Protective role of heme oxyge-nase-1 in oxidative stress-induced neuronal injury. J Neu-rosci Res 1999;56:652-658.
115. Nakatani, N. Phenolic antioxidants from herbs and spices. Biofactors 2000;13:141-146.
116. Gómez-Pinilla, F. Brain foods: The effects of nutrients on brain function. Nat Rev Neurosci 2008;9:568-578.
117. Ammon HPT, Wahl MA. Pharmacology of Curcuma Longa. Planta Med 1991;57:1-7.
118. Priyadarsini KI, Guha SN, Rao MN. Physico-chemical properties and antioxidant activities of methoxy phenols. Free Radic Biol Med1998;24:933-941.
119. Martin-Aragon S, Benedi JM, Villar AM. Modifications on antioxidant capacity and lipid peroxidation in mice under fraxetin treatment. J Pharm Pharmacol 1997;49:49-52.
120. Sreejayan A, Rao MN. Nitric oxide scavenging by curcu-minoids. J Pharm Pharmacol 1997;49:105-107.
121. Masuda T, Hidaka K, Shinohara A, Maekawa T, Takeda Y, Yamaguchi H. Chemical studies on antioxidant mechanism of curcuminoid: analysis of radical reaction products from curcumin. J Agric Food Chem 1999;47:71-77.
122. Jovanovic SV, Boone CW, Steenken S, Trinoga M, Kaskey RB. How curcumin works preferentially with soluble an-tioxidants. J Am Chem Soc 2001;123:3064-3068.
123. Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yama-moto M, Talalay P, Kensler TW. Sensitivity to carcinogen-esis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci USA 2001;98:3410-3415.
124. Singh S, Aggarwal BB. Activation of transcription factor NF-kB is suppressed by curcumin (diferuloylmethane). J Biol Chem 1995;270:24995-25000.
125. Huang MT, Newmark HL, Frenkel K. Inhibitory effects of curcumin on tumorigenesis in mice. J Cell Biochem Suppl 1997;27:26-34.
126. Abe Y, Hashimoto S, Horie T. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 1999;39:41-47.
127. Awasthi S, Pandya U, Singhal SS, Lin JT, Thiviyanathan V, Seifert WE, Jr Awasthi YC, Ansari GA. Curcumin-glutathione interactions and the role of human glutathione S-transferase P1-1. Chem Biol Interact 2000;128:19-38.
128. Singhal SS, Awasthi S, Pandya U, Piper JT, Saini MK, Cheng JZ, Awasthi YC. The effect of curcumin on gluta-thione-linked enzymes in K562 human leukemia cells. Toxicol Lett 1999;109:87-95.
129. Motterlini R, Foresti R, Bassi R, Green CJ. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000;28:1303-1312.
130. Scapagnini G, Foresti R, Calabrese V, Giuffrida Stella AM, Green CJ, Motterlini R. Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 2002;61:554-561.
131. Scapagnini G, Colombrita C, Amadio M, D'Agata V, Arcelli E, Sapienza M, Calabrese V. Curcumin activates defensive genes and protects neurons against oxidative stress. Anti-oxid Redox Signal 2006;8:395-403.
132. Scapagnini G, Calabrese V, Motterlini R, Colombrita C, Alkon DL. Use of curcumin derivatives or CAPE in the manufacture of a medicament for the treatment of neuro-protective disorders. World Patent Number: WO 2004= 075883 A1, Publication date: 2004-2009-10.
133. Goel, A, Kunnumakkara AB, Aggarwal BB. Curcumin as "Curecumin": From kitchen to clinic. Biochem Pharmacol 2008;75:787-809.
134. Rajakrishnan V, Viswanathan P, Rajasekharan KN, Menon VP. Neuroprotective role of curcumin from curcuma longa on ethanolinduced brain damage. Phytother Res 1999; 13:571-574.
135. Chandra V, Pandav R, Dodge HH, Johnston JM, Belle SH, DeKosky ST. Incidence of Alzheimer's disease in a rural community in India: The Indo-US study. Neurology 2001; 57:985-989.
136. Ng TP, Chiam PC, Lee T, Chua HC, Lim L, Kua EH. Curry consumption and cognitive function in the elderly. Am J Epidemiol 2006;164:898-906.
137. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001;21:8370-8377.
138. Frautschy SA, Hu W, Miller SA, Kim P, Harris-White ME, Cole GM. Phenolic anti-inflammatory antioxidant reversal of Ab-induced cognitive deficits and neuropathology. Neurobiol Aging 2001;22:993-1005.
139. Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 2005;280:5892-5901.
140. Cole GM, Teter B, Frautschy SA. Neuroprotective effects of curcumin. Adv Exp Med Biol 2007;595:197-212.
141. Baum L, Lam CW, Cheung SK, Kwok T, Lui V, Tsoh J, Lam L, Leung V, Hui E, Ng C, Woo J, Chiu HF, Goggins WB, Zee BC, Cheng KF, Fong CY, Wong A, Mok H, Chow MS, Ho PC, Ip SP, Ho CS, Yu XW, Lai CY, Chan MH, Szeto S, Chan IH, Mok V. Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease. J Clin Psychopharmacol 2008;28:110-113.
142. Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA. Curcumin structure-function, bioavailability, and efficacy in models of neuro-inflammation and Alzheimer's disease. J Pharmacol Exp Ther 2008;326:196-208.
143. Martin, D, Rojo AI, Salinas M, Diaz R, Gallardo G, Alam J, De Galarreta CM, Cuadrado A. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase=Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 2004;279:8919-8929.
144. Surh YJ, Kundu JK, Na HK. Nrf2 as a master redox switch in turning on the cellular signaling involved in the induction of cytoprotective genes by some chemopreventive phytochemicals. Planta Med 2008;74:1526-1539.
145. Zhuang H, Kim YS, Koehler RC, Dore S. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann NY Acad Sci 2003;993:276-286.
146. Foresti R, Hoque M, Monti D, Green CJ, Motterlini R. Differential activation of heme oxygenase-1 by chalcones and rosolic acid in endothelial cells. J Pharmacol Exp Ther 2005;312:686-693.
147. Talalay P, Fahey JW, Healy ZR, Wehage SL, Benedict AL, Min C, Dinkova-Kostova AT. Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc Natl Acad Sci USA 2007;104:17500-117005
148. Scapagnini G, Butterfield DA, Colombrita C, Sultana R, Pascale A, Calabrese V. Ethyl ferulate, a lipophilic poly-phenol, induces HO-1 and protects rat neurons against oxidative stress. Antioxid Redox Signal 2004;6:811-818.
149. Kweon M.H, Adhami VM, Lee JS, Mukhtarm H. Constitutive overexpression of Nrf2-dependent heme oxygenase-1 in A549 cells contributes to resistance to apo-ptosis induced by epigallocatechin 3-gallate. J Biol Chem 2006;281:33761-33772.