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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 863))

Abstract

Alzheimer’s disease (AD) is an insidious neurological disorder that affects memory, one of the human brain’s main cognitive functions. Around 5.2 million Americans currently have AD, and the number threatens to climb to 7 million by 2020. Our native country, Colombia, is no exception with an estimated 260,000 individuals to be affected by AD in 2020. A large, genetically-isolated community in Antioquia, Colombia, with early-onset familial Alzheimer’s disease due to a presenilin-1 mutation is ideally suited for the study of molecular mechanisms of AD, and hence accelerate the discovery of new or alternative treatment approaches. In this regard, polyphenols – also known as polyhydroxyphenols – have shown antioxidant activity, gene regulation, metal chelator and anti-amyloidogenic aggregation effects. However, further in vitro and in vivo investigations are warranted to validate their use in clinical trials. Drosophila melanogaster is increasingly being used as a valid in vivo model of AD. Here, we summarise data published within the past 16 years (1998–2014) on the molecular biology of AD and the use of polyphenols in the fly to understand the molecular actions and feasibility of these compounds in the treatment of AD.

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References

  • Abdelwahid E, Rolland S, Teng X, Conradt B, Hardwick JM, White K (2011) Mitochondrial involvement in cell death of non-mammalian eukaryotes. Biochim Biophys Acta 1813(4):597–607. doi:10.1016/j.bbamcr.2010.10.008

    CAS  PubMed Central  PubMed  Google Scholar 

  • Abramov AY, Canevari L, Duchen MR (2004) Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci 24(2):565–575. doi:10.1523/JNEUROSCI.4042-03.2004

    CAS  PubMed  Google Scholar 

  • Acosta-Baena N, Sepulveda-Falla D, Lopera-Gomez CM, Jaramillo-Elorza MC, Moreno S, Aguirre-Acevedo DC, Saldarriaga A, Lopera F (2011) Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer’s disease: a retrospective cohort study. Lancet Neurol 10(3):213–220. doi:10.1016/S1474-4422(10)70323-9

    CAS  PubMed  Google Scholar 

  • Aisen PS (2009) Alzheimer’s disease therapeutic research: the path forward. Alzheimers Res Ther 1(1):2. doi:10.1186/alzrt2

    PubMed Central  PubMed  Google Scholar 

  • Ali YO, Escala W, Ruan K, Zhai RG (2011) Assaying locomotor, learning, and memory deficits in Drosophila models of neurodegeneration. J Vis Exp (49). pii: 2504. doi:10.3791/2504

  • Aliev G, Obrenovich ME, Reddy VP, Shenk JC, Moreira PI, Nunomura A, Zhu X, Smith MA, Perry G (2008) Antioxidant therapy in Alzheimer’s disease: theory and practice. Mini Rev Med Chem 8(13):1395–1406

    CAS  PubMed Central  PubMed  Google Scholar 

  • Alzheimer (Munich): about a peculiar disease of the cerebral cortex (2000) Paper presented at the 37th meeting of Psychiatrists of Southwestern Germany, Tubingen, 3rd and 4th Nov 1906

    Google Scholar 

  • Alzheimer’s Disease Collaborative G (1995) The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet 11(2):219–222. doi:10.1038/ng1095-219

    Google Scholar 

  • Ansari N, Khodagholi F (2013) Natural products as promising drug candidates for the treatment of Alzheimer’s disease: molecular mechanism aspect. Curr Neuropharmacol 11(4):414–429. doi:10.2174/1570159X11311040005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Arcos-Burgos M, Muenke M (2002) Genetics of population isolates. Clin Genet 61(4):233–247

    CAS  PubMed  Google Scholar 

  • Ayutyanont N, Langbaum JB, Hendrix SB, Chen K, Fleisher AS, Friesenhahn M, Ward M, Aguirre C, Acosta-Baena N, Madrigal L, Muñoz C, Tirado V, Moreno S, Tariot PN, Lopera F, Reiman EM (2014) The alzheimer’s prevention initiative composite cognitive test score: sample size estimates for the evaluation of preclinical alzheimer’s disease treatments in presenilin 1 E280A mutation carriers. J Clin Psychiatry 75(6):652–660. doi:10.4088/JCP.13m08927

    PubMed Central  PubMed  Google Scholar 

  • Barco A, Bailey CH, Kandel ER (2006) Common molecular mechanisms in explicit and implicit memory. J Neurochem 97(6):1520–1533. doi:10.1111/j.1471-4159.2006.03870.x

    CAS  PubMed  Google Scholar 

  • Barone E, Di Domenico F, Butterfield DA (2014) Statins more than cholesterol lowering agents in Alzheimer disease: their pleiotropic functions as potential therapeutic targets. Biochem Pharmacol 88(4):605–616. doi:10.1016/j.bcp.2013.10.030

    CAS  PubMed Central  PubMed  Google Scholar 

  • Baulac S, Lu H, Strahle J, Yang T, Goldberg MS, Shen J, Schlossmacher MG, Lemere CA, Lu Q, Xia W (2009) Increased DJ-1 expression under oxidative stress and in Alzheimer’s disease brains. Mol Neurodegener 4:12. doi:10.1186/1750-1326-4-12

    PubMed Central  PubMed  Google Scholar 

  • Bayer TA, Wirths O (2014) Focusing the amyloid cascade hypothesis on N-truncated Abeta peptides as drug targets against Alzheimer’s disease. Acta Neuropathol 127(6):787–801. doi:10.1007/s00401-014-1287-x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Beckett C, Nalivaeva NN, Belyaev ND, Turner AJ (2012) Nuclear signalling by membrane protein intracellular domains: the AICD enigma. Cell Signal 24(2):402–409. doi:10.1016/j.cellsig.2011.10.007

    CAS  PubMed  Google Scholar 

  • Behl C, Davis JB, Lesley R, Schubert D (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77(6):817–827

    CAS  PubMed  Google Scholar 

  • Berry JA, Cervantes-Sandoval I, Nicholas EP, Davis RL (2012) Dopamine is required for learning and forgetting in Drosophila. Neuron 74(3):530–542. doi:10.1016/j.neuron.2012.04.007

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bettens K, Sleegers K, Van Broeckhoven C (2010) Current status on Alzheimer disease molecular genetics: from past, to present, to future. Hum Mol Genet 19(R1):R4–R11. doi:10.1093/hmg/ddq142

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bobes MA, Garcia YF, Lopera F, Quiroz YT, Galan L, Vega M, Trujillo N, Valdes-Sosa M, Valdes-Sosa P (2010) ERP generator anomalies in presymptomatic carriers of the Alzheimer’s disease E280A PS-1 mutation. Hum Brain Mapp 31(2):247–265. doi:10.1002/hbm.20861

    PubMed  Google Scholar 

  • Bonilla-Ramirez L, Jimenez-Del-Rio M, Velez-Pardo C (2011) Acute and chronic metal exposure impairs locomotion activity in Drosophila melanogaster: a model to study Parkinsonism. Biometals 24(6):1045–1057. doi:10.1007/s10534-011-9463-0

    CAS  PubMed  Google Scholar 

  • Bonilla-Ramirez L, Jimenez-Del-Rio M, Velez-Pardo C (2014) Efecto del flavanol EGCG y Curcuminoides en Drosophila melanogaster que expresa Ab1-42-TAU: modelo de neuroproteccion en la enfermedad de Alzheimer. [Effect of the flavanol EGCG and Curcuminoids in Drosophila melanogaster which expresses Ab1-42-TAU: neuroprotection model in Alzheimer’s disease]. Paper presented at the IX Congreso Nacional de Neurociencias/X Seminario Internacional de Neurociencias, Cartagena, 15–17 May 2014

    Google Scholar 

  • Boutajangout A, Wisniewski T (2014) Tau-based therapeutic approaches for Alzheimer’s disease – a mini-review. Gerontology. doi:10.1159/000358875

    PubMed Central  PubMed  Google Scholar 

  • Burgold S, Filser S, Dorostkar MM, Schmidt B, Herms J (2014) In vivo imaging reveals sigmoidal growth kinetic of β-amyloid plaques. Acta Neuropathol Commun 2(1):30. doi:10.1186/2051-5960-2-30

    PubMed Central  PubMed  Google Scholar 

  • Butterfield DA, Sultana R (2011) Methionine-35 of aβ(1–42): importance for oxidative stress in Alzheimer disease. J Amino Acids 2011:198430. doi:10.4061/2011/198430

    PubMed Central  PubMed  Google Scholar 

  • Butterfield DA, Drake J, Pocernich C, Castegna A (2001) Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 7(12):548–554

    CAS  PubMed  Google Scholar 

  • Butterfield DA, Swomley AM, Sultana R (2013) Amyloid β-peptide (1–42)-induced oxidative stress in Alzheimer disease: importance in disease pathogenesis and progression. Antioxid Redox Signal 19(8):823–835. doi:10.1089/ars.2012.5027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Caesar I, Jonson M, Nilsson KP, Thor S, Hammarström P (2012) Curcumin promotes A-beta fibrillation and reduces neurotoxicity in transgenic Drosophila. PLoS One 7(2), e31424. doi:10.1371/journal.pone.0031424

    CAS  PubMed Central  PubMed  Google Scholar 

  • Campbell RA, Turner GC (2010) The mushroom body. Curr Biol 20(1):R11–R12. doi:10.1016/j.cub.2009.10.031

    CAS  PubMed  Google Scholar 

  • Capetillo-Zarate E, Gracia L, Tampellini D, Gouras GK (2012) Intraneuronal Aβ accumulation, amyloid plaques, and synapse pathology in Alzheimer’s disease. Neurodegener Dis 10(1–4):56–59. doi:10.1159/000334762

    CAS  PubMed  Google Scholar 

  • Carmine-Simmen K, Proctor T, Tschäpe J, Poeck B, Triphan T, Strauss R, Kretzschmar D (2009) Neurotoxic effects induced by the Drosophila amyloid-beta peptide suggest a conserved toxic function. Neurobiol Dis 33(2):274–281. doi:10.1016/j.nbd.2008.10.014

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cash DM, Ridgway GR, Liang Y, Ryan NS, Kinnunen KM, Yeatman T, Malone IB, Benzinger TL, Jack CR, Thompson PM, Ghetti BF, Saykin AJ, Masters CL, Ringman JM, Salloway SP, Schofield PR, Sperling RA, Cairns NJ, Marcus DS, Xiong C, Bateman RJ, Morris JC, Rossor MN, Ourselin S, Fox NC, (DIAN) DIAN (2013) The pattern of atrophy in familial Alzheimer disease: volumetric MRI results from the DIAN study. Neurology 81(16):1425–1433. doi:10.1212/WNL.0b013e3182a841c6

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cenini G, Sultana R, Memo M, Butterfield DA (2008) Elevated levels of pro-apoptotic p53 and its oxidative modification by the lipid peroxidation product, HNE, in brain from subjects with amnestic mild cognitive impairment and Alzheimer’s disease. J Cell Mol Med 12(3): 987–994. doi:10.1111/j.1582-4934.2008.00163.x

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chabrier MA, Blurton-Jones M, Agazaryan AA, Nerhus JL, Martinez-Coria H, LaFerla FM (2012) Soluble aβ promotes wild-type tau pathology in vivo. J Neurosci 32(48):17345–17350. doi:10.1523/JNEUROSCI.0172-12.2012

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chakraborty R, Vepuri V, Mhatre SD, Paddock BE, Miller S, Michelson SJ, Delvadia R, Desai A, Vinokur M, Melicharek DJ, Utreja S, Khandelwal P, Ansaloni S, Goldstein LE, Moir RD, Lee JC, Tabb LP, Saunders AJ, Marenda DR (2011) Characterization of a Drosophila Alzheimer’s disease model: pharmacological rescue of cognitive defects. PLoS One 6(6), e20799. doi:10.1371/journal.pone.0020799

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chan KY, Wang W, Wu JJ, Liu L, Theodoratou E, Car J, Middleton L, Russ TC, Deary IJ, Campbell H, Rudan I, Global Health Epidemiology Reference Group (GHERG) (2013) Epidemiology of Alzheimer’s disease and other forms of dementia in China, 1990–2010: a systematic review and analysis. Lancet 381(9882):2016–2023. doi:10.1016/S0140-6736(13)60221-4

    PubMed  Google Scholar 

  • Choi J, Sullards MC, Olzmann JA, Rees HD, Weintraub ST, Bostwick DE, Gearing M, Levey AI, Chin LS, Li L (2006) Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J Biol Chem 281(16):10816–10824. doi:10.1074/jbc.M509079200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cipriani G, Dolciotti C, Picchi L, Bonuccelli U (2011) Alzheimer and his disease: a brief history. Neurol Sci 32(2):275–279. doi:10.1007/s10072-010-0454-7

    PubMed  Google Scholar 

  • Cornejo W, Lopera F, Uribe C, Salinas M (1987) Description of a family affected by Alzheimer type presenile dementia. Acta Med Col 12:55–61

    Google Scholar 

  • Crouch PJ, Harding SM, White AR, Camakaris J, Bush AI, Masters CL (2008) Mechanisms of A beta mediated neurodegeneration in Alzheimer’s disease. Int J Biochem Cell Biol 40(2):181–198. doi:10.1016/j.biocel.2007.07.013

    CAS  PubMed  Google Scholar 

  • Crowther DC, Kinghorn KJ, Miranda E, Page R, Curry JA, Duthie FA, Gubb DC, Lomas DA (2005) Intraneuronal Abeta, non-amyloid aggregates and neurodegeneration in a Drosophila model of Alzheimer’s disease. Neuroscience 132(1):123–135. doi:10.1016/j.neuroscience.2004.12.025

    CAS  PubMed  Google Scholar 

  • De Strooper B (2003) Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 38(1):9–12

    PubMed  Google Scholar 

  • De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391(6665):387–390. doi:10.1038/34910

    PubMed  Google Scholar 

  • De Strooper B, Vassar R, Golde T (2010) The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat Rev Neurol 6(2):99–107. doi:10.1038/nrneurol.2009.218

    PubMed Central  PubMed  Google Scholar 

  • De Strooper B, Iwatsubo T, Wolfe MS (2012) Presenilins and γ-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harb Perspect Med 2(1):a006304. doi:10.1101/cshperspect.a006304

    PubMed Central  PubMed  Google Scholar 

  • Dean DC, Jerskey BA, Chen K, Protas H, Thiyyagura P, Roontiva A, O’Muircheartaigh J, Dirks H, Waskiewicz N, Lehman K, Siniard AL, Turk MN, Hua X, Madsen SK, Thompson PM, Fleisher AS, Huentelman MJ, Deoni SC, Reiman EM (2014) Brain differences in infants at differential genetic risk for late-onset Alzheimer disease: a cross-sectional imaging study. JAMA Neurol 71(1):11–22. doi:10.1001/jamaneurol.2013.4544

    PubMed Central  PubMed  Google Scholar 

  • Debnath T, Park P, Deb Nath N, Samad N, Park H, Lim B (2011) Antioxidant activity of Gardenia jasminoides Ellis fruit extracts. Food Chem 128(3):697–703

    CAS  Google Scholar 

  • Drachman DA (2014) The amyloid hypothesis, time to move on: amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement 10(3):372–380. doi:10.1016/j.jalz.2013.11.003

    PubMed  Google Scholar 

  • Ebstein RP, Nemanov L, Lubarski G, Dano M, Trevis T, Korczyn AD (1996) Changes in expression of lymphocyte amyloid precursor protein mRNA isoforms in normal aging and Alzheimer’s disease. Brain Res Mol Brain Res 35(1–2):260–268

    CAS  PubMed  Google Scholar 

  • Elliott DA, Brand AH (2008) The GAL4 system : a versatile system for the expression of genes. Methods Mol Biol 420:79–95. doi:10.1007/978-1-59745-583-1_5

    CAS  PubMed  Google Scholar 

  • Esiri M (2001) The neuropathology of Alzheimer’s disease. In: Dawbarn D, Allen S (eds) Neurobiology of Alzheimer’s disease. Oxford University Press, New York, pp 33–53

    Google Scholar 

  • Fargo K, Bleiler L (2014) Alzheimer’s Association report. Alzheimers Dement 10(2):e47–e92

    Google Scholar 

  • Fettelschoss A, Zabel F, Bachmann MF (2014) Vaccination against Alzheimer disease: an update on future strategies. Hum Vaccin Immunother 10(4)

    Google Scholar 

  • Fleisher AS, Chen K, Quiroz YT, Jakimovich LJ, Gomez MG, Langois CM, Langbaum JB, Ayutyanont N, Roontiva A, Thiyyagura P, Lee W, Mo H, Lopez L, Moreno S, Acosta-Baena N, Giraldo M, Garcia G, Reiman RA, Huentelman MJ, Kosik KS, Tariot PN, Lopera F, Reiman EM (2012) Florbetapir PET analysis of amyloid-β deposition in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: a cross-sectional study. Lancet Neurol 11(12):1057–1065. doi:10.1016/S1474-4422(12)70227-2

    CAS  PubMed  Google Scholar 

  • Folwell J, Cowan CM, Ubhi KK, Shiabh H, Newman TA, Shepherd D, Mudher A (2010) Abeta exacerbates the neuronal dysfunction caused by human tau expression in a Drosophila model of Alzheimer’s disease. Exp Neurol 223(2):401–409. doi:10.1016/j.expneurol.2009.09.014

    CAS  PubMed  Google Scholar 

  • Foucaud J, Burns JG, Mery F (2010) Use of spatial information and search strategies in a water maze analog in Drosophila melanogaster. PLoS One 5(12), e15231. doi:10.1371/journal.pone.0015231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fraga CG, Galleano M, Verstraeten SV, Oteiza PI (2010) Basic biochemical mechanisms behind the health benefits of polyphenols. Mol Aspects Med 31(6):435–445. doi:10.1016/j.mam.2010.09.006

    CAS  PubMed  Google Scholar 

  • Frank DA, Greenberg ME (1994) CREB: a mediator of long-term memory from mollusks to mammals. Cell 79(1):5–8

    CAS  PubMed  Google Scholar 

  • Frautschy SA, Cole GM (2010) Why pleiotropic interventions are needed for Alzheimer’s disease. Mol Neurobiol 41(2–3):392–409. doi:10.1007/s12035-010-8137-1

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fu Y, Maianu L, Melbert BR, Garvey WT (2004) Facilitative glucose transporter gene expression in human lymphocytes, monocytes, and macrophages: a role for GLUT isoforms 1, 3, and 5 in the immune response and foam cell formation. Blood Cells Mol Dis 32(1):182–190

    CAS  PubMed  Google Scholar 

  • Fuchs SY, Adler V, Pincus MR, Ronai Z (1998) MEKK1/JNK signaling stabilizes and activates p53. Proc Natl Acad Sci U S A 95(18):10541–10546

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gaeta A, Hider RC (2005) The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. Br J Pharmacol 146(8):1041–1059. doi:10.1038/sj.bjp.0706416

    CAS  PubMed Central  PubMed  Google Scholar 

  • Galleano M, Verstraeten SV, Oteiza PI, Fraga CG (2010) Antioxidant actions of flavonoids: thermodynamic and kinetic analysis. Arch Biochem Biophys 501(1):23–30. doi:10.1016/j.abb.2010.04.005

    CAS  PubMed  Google Scholar 

  • Gao J, Inagaki Y, Li X, Kokudo N, Tang W (2013) Research progress on natural products from traditional Chinese medicine in treatment of Alzheimer’s disease. Drug Discov Ther 7(2):46–57

    CAS  PubMed  Google Scholar 

  • García-Ospina GP, Jímenez-Del Río M, Lopera F, Vélez-Pardo C (2003) Neuronal DNA damage correlates with a positive detection of c-Jun, nuclear factor kB, p53 and Par-4 transcription factors in Alzheimer’s disease. Rev Neurol 36(11):1004–1010

    PubMed  Google Scholar 

  • Ghosh AK, Osswald HL (2014) BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem Soc Rev. doi:10.1039/c3cs60460h

    PubMed  Google Scholar 

  • Giacobini E, Gold G (2013) Alzheimer disease therapy – moving from amyloid-β to tau. Nat Rev Neurol 9(12):677–686. doi:10.1038/nrneurol.2013.223

    CAS  PubMed  Google Scholar 

  • Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120(3):885–890

    CAS  PubMed  Google Scholar 

  • Goate A, Chartier-Harlin MC, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349(6311):704–706. doi:10.1038/349704a0

    CAS  PubMed  Google Scholar 

  • Goedert M, Hasegawa M, Jakes R, Lawler S, Cuenda A, Cohen P (1997) Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases. FEBS Lett 409(1):57–62

    CAS  PubMed  Google Scholar 

  • Golde TE (2009) The therapeutic importance of understanding mechanisms of neuronal cell death in neurodegenerative disease. Mol Neurodegener 4:8. doi:10.1186/1750-1326-4-8

    PubMed Central  PubMed  Google Scholar 

  • Golde TE, Dickson D, Hutton M (2006) Filling the gaps in the abeta cascade hypothesis of Alzheimer’s disease. Curr Alzheimer Res 3(5):421–430

    CAS  PubMed  Google Scholar 

  • Golde TE, Schneider LS, Koo EH (2011) Anti-aβ therapeutics in Alzheimer’s disease: the need for a paradigm shift. Neuron 69(2):203–213. doi:10.1016/j.neuron.2011.01.002

    CAS  PubMed Central  PubMed  Google Scholar 

  • Götz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293(5534):1491–1495. doi:10.1126/science.1062097

    PubMed  Google Scholar 

  • Graeber MB, Kösel S, Grasbon-Frodl E, Möller HJ, Mehraein P (1998) Histopathology and APOE genotype of the first Alzheimer disease patient, Auguste D. Neurogenetics 1(3):223–228

    CAS  PubMed  Google Scholar 

  • Greenough MA, Camakaris J, Bush AI (2013) Metal dyshomeostasis and oxidative stress in Alzheimer’s disease. Neurochem Int 62(5):540–555. doi:10.1016/j.neuint.2012.08.014

    CAS  PubMed  Google Scholar 

  • Greeve I, Kretzschmar D, Tschäpe JA, Beyn A, Brellinger C, Schweizer M, Nitsch RM, Reifegerste R (2004) Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila. J Neurosci 24(16):3899–3906. doi:10.1523/JNEUROSCI.0283-04.2004

    CAS  PubMed  Google Scholar 

  • Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM (1986) Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 261(13):6084–6089

    CAS  PubMed  Google Scholar 

  • Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Dérijard B, Davis RJ (1996) Selective interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15(11):2760–2770

    CAS  PubMed Central  PubMed  Google Scholar 

  • Haass C (2004) Take five – BACE and the gamma-secretase quartet conduct Alzheimer’s amyloid beta-peptide generation. EMBO J 23(3):483–488. doi:10.1038/sj.emboj.7600061

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hardy J (2006) Has the amyloid cascade hypothesis for Alzheimer’s disease been proved? Curr Alzheimer Res 3(1):71–73

    CAS  PubMed  Google Scholar 

  • Hardy J (2009) The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal. J Neurochem 110(4):1129–1134. doi:10.1111/j.1471-4159.2009.06181.x

    CAS  PubMed  Google Scholar 

  • Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054):184–185

    CAS  PubMed  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356. doi:10.1126/science.1072994

    CAS  PubMed  Google Scholar 

  • He X, Park HM, Hyung SJ, DeToma AS, Kim C, Ruotolo BT, Lim MH (2012) Exploring the reactivity of flavonoid compounds with metal-associated amyloid-β species. Dalton Trans 41(21):6558–6566. doi:10.1039/c2dt12207c

    CAS  PubMed  Google Scholar 

  • Hebert LE, Weuve J, Scherr PA, Evans DA (2013) Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology 80(19):1778–1783. doi:10.1212/WNL.0b013e31828726f5

    PubMed Central  PubMed  Google Scholar 

  • Herrera-Rivero M, Soto-Cid A, Hernández ME, Aranda-Abreu GE (2013) Tau, APP, NCT and BACE1 in lymphocytes through cognitively normal ageing and neuropathology. An Acad Bras Cienc 85(4):1489–1496. doi:10.1590/0001-376520130013

    CAS  PubMed  Google Scholar 

  • Hider RC, Liu ZD, Khodr HH (2001) Metal chelation of polyphenols. Methods Enzymol 335:190–203

    CAS  PubMed  Google Scholar 

  • Hirohata M, Ono K, Takasaki J, Takahashi R, Ikeda T, Morinaga A, Yamada M (2012) Anti-amyloidogenic effects of soybean isoflavones in vitro: fluorescence spectroscopy demonstrating direct binding to Aβ monomers, oligomers and fibrils. Biochim Biophys Acta 1822(8):1316–1324. doi:10.1016/j.bbadis.2012.05.006

    CAS  PubMed  Google Scholar 

  • Hong YK, Park SH, Lee S, Hwang S, Lee MJ, Kim D, Lee JH, Han SY, Kim ST, Kim YK, Jeon S, Koo BS, Cho KS (2011) Neuroprotective effect of SuHeXiang Wan in Drosophila models of Alzheimer’s disease. J Ethnopharmacol 134(3):1028–1032. doi:10.1016/j.jep.2011.02.012

    PubMed  Google Scholar 

  • Hu Y, Fortini ME (2003) Different cofactor activities in gamma-secretase assembly: evidence for a nicastrin-Aph-1 subcomplex. J Cell Biol 161(4):685–690. doi:10.1083/jcb.200304014

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huang Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX (2005) NF-kappaB precursor, p105, and NF-kappaB inhibitor, IkappaBgamma, are both elevated in Alzheimer disease brain. Neurosci Lett 373(2):115–118. doi:10.1016/j.neulet.2004.09.074

    CAS  PubMed  Google Scholar 

  • Hubin E, van Nuland NA, Broersen K, Pauwels K (2014) Transient dynamics of Aβ contribute to toxicity in Alzheimer’s disease. Cell Mol Life Sci. doi:10.1007/s00018-014-1634-z

    PubMed Central  PubMed  Google Scholar 

  • Iijima K, Gatt A, Iijima-Ando K (2010) Tau Ser262 phosphorylation is critical for Abeta42-induced tau toxicity in a transgenic Drosophila model of Alzheimer’s disease. Hum Mol Genet 19(15):2947–2957. doi:10.1093/hmg/ddq200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iijima-Ando K, Iijima K (2010) Transgenic Drosophila models of Alzheimer’s disease and tauopathies. Brain Struct Funct 214(2–3):245–262. doi:10.1007/s00429-009-0234-4

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iqbal K, Alonso A, Gong C, Khatoon S, Kudo T, Singh T, Grundke-Iqbal I (1993) Molecular pathology of Alzheimer neurofibrillary degeneration. Acta Neurobiol Exp (Wars) 53(1):325–335

    CAS  Google Scholar 

  • Jahn TR, Kohlhoff KJ, Scott M, Tartaglia GG, Lomas DA, Dobson CM, Vendruscolo M, Crowther DC (2011) Detection of early locomotor abnormalities in a Drosophila model of Alzheimer’s disease. J Neurosci Methods 197(1):186–189. doi:10.1016/j.jneumeth.2011.01.026

    PubMed Central  PubMed  Google Scholar 

  • Jänicke RU, Sprengart ML, Wati MR, Porter AG (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273(16):9357–9360

    PubMed  Google Scholar 

  • Jimenez Del Rio M, Velez-Pardo C (2006) Insulin-like growth factor-1 prevents Abeta[25–35]/(H2O2)-induced apoptosis in lymphocytes by reciprocal NF-kappaB activation and p53 inhibition via PI3K-dependent pathway. Growth Factors 24(1):67–78. doi:10.1080/08977190500361788

    CAS  PubMed  Google Scholar 

  • Jimenez-Del-Rio M, Velez-Pardo C (2004) The hydrogen peroxide and its importance in Alzheimer’s and Parkinson’s disease. Curr Med Chem 4:279–285

    Google Scholar 

  • Jimenez-Del-Rio M, Velez-Pardo C (2012) The bad, the good, and the ugly about oxidative stress. Oxid Med Cell Longev 2012:163913. doi:10.1155/2012/163913

    PubMed Central  PubMed  Google Scholar 

  • Jimenez-Del-Rio M, Daza-Restrepo A, Velez-Pardo C (2008) The cannabinoid CP55,940 prolongs survival and improves locomotor activity in Drosophila melanogaster against paraquat: implications in Parkinson’s disease. Neurosci Res 61(4):404–411. doi:10.1016/j.neures.2008.04.011

    CAS  PubMed  Google Scholar 

  • Jimenez-Del-Rio M, Guzman-Martinez C, Velez-Pardo C (2010) The effects of polyphenols on survival and locomotor activity in Drosophila melanogaster exposed to iron and paraquat. Neurochem Res 35(2):227–238. doi:10.1007/s11064-009-0046-1

    CAS  PubMed  Google Scholar 

  • Jung Y, Kim H, Min SH, Rhee SG, Jeong W (2008) Dynein light chain LC8 negatively regulates NF-kappaB through the redox-dependent interaction with IkappaBalpha. J Biol Chem 283(35):23863–23871. doi:10.1074/jbc.M803072200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaminsky YG, Marlatt MW, Smith MA, Kosenko EA (2010) Subcellular and metabolic examination of amyloid-beta peptides in Alzheimer disease pathogenesis: evidence for Abeta(25–35). Exp Neurol 221(1):26–37. doi:10.1016/j.expneurol.2009.09.005

    CAS  PubMed  Google Scholar 

  • Kandel ER (2012) The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 5:14. doi:10.1186/1756-6606-5-14

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kandel ER, Dudai Y, Mayford MR (2014) The molecular and systems biology of memory. Cell 157(1):163–186. doi:10.1016/j.cell.2014.03.001

    CAS  PubMed  Google Scholar 

  • Karran E, Mercken M, De Strooper B (2011) The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. Nat Rev Drug Discov 10(9):698–712. doi:10.1038/nrd3505

    CAS  PubMed  Google Scholar 

  • Khan A, Dobson JP, Exley C (2006) Redox cycling of iron by Abeta42. Free Radic Biol Med 40(4):557–569. doi:10.1016/j.freeradbiomed.2005.09.013

    CAS  PubMed  Google Scholar 

  • Kim HG, Oh MS (2012) Herbal medicines for the prevention and treatment of Alzheimer’s disease. Curr Pharm Des 18(1):57–75

    CAS  PubMed  Google Scholar 

  • Kim J, Lee HJ, Lee KW (2010) Naturally occurring phytochemicals for the prevention of Alzheimer’s disease. J Neurochem 112(6):1415–1430. doi:10.1111/j.1471-4159.2009.06562.x

    CAS  PubMed  Google Scholar 

  • Kim T, Vidal GS, Djurisic M, William CM, Birnbaum ME, Garcia KC, Hyman BT, Shatz CJ (2013) Human LilrB2 is a β-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer’s model. Science 341(6152):1399–1404. doi:10.1126/science.1242077

    CAS  PubMed  Google Scholar 

  • Kimberly WT, Esler WP, Ye W, Ostaszewski BL, Gao J, Diehl T, Selkoe DJ, Wolfe MS (2003a) Notch and the amyloid precursor protein are cleaved by similar gamma-secretase(s). Biochemistry 42(1):137–144. doi:10.1021/bi026888g

    CAS  PubMed  Google Scholar 

  • Kimberly WT, LaVoie MJ, Ostaszewski BL, Ye W, Wolfe MS, Selkoe DJ (2003b) Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A 100(11):6382–6387. doi:10.1073/pnas.1037392100

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klünemann HH, Fronhöfer W, Wurster H, Fischer W, Ibach B, Klein HE (2002) Alzheimer’s second patient: Johann F. and his family. Ann Neurol 52(4):520–523. doi:10.1002/ana.10309

    PubMed  Google Scholar 

  • Kooijman R, Willems M, De Haas CJ, Rijkers GT, Schuurmans AL, Van Buul-Offers SC, Heijnen CJ, Zegers BJ (1992) Expression of type I insulin-like growth factor receptors on human peripheral blood mononuclear cells. Endocrinology 131(5):2244–2250. doi:10.1210/endo.131.5.1425423

    CAS  PubMed  Google Scholar 

  • Korczyn AD (2008) The amyloid cascade hypothesis. Alzheimers Dement 4(3):176–178. doi:10.1016/j.jalz.2007.11.008

    CAS  PubMed  Google Scholar 

  • Kosik KS, Munoz C, Lopez L, Arcila ML, Garcia G, Madrigal L, Moreno S, Rios Romenets S, Lopez H, Gutierrez M, Langbaum JB, Cho W, Suliman S, Tariot PN, Ho C, Reiman EM, Lopera F (2015) Homozygosity of the autosomal dominant Alzheimer disease presenilin 1 E280A mutation. Neurology 84(2):206–208.doi:10.1212/WNL.0000000000001130

    PubMed  Google Scholar 

  • Kostomoiri M, Fragkouli A, Sagnou M, Skaltsounis LA, Pelecanou M, Tsilibary EC, Tzinia AK (2013) Oleuropein, an anti-oxidant polyphenol constituent of olive promotes α-secretase cleavage of the amyloid precursor protein (AβPP). Cell Mol Neurobiol 33(1):147–154. doi:10.1007/s10571-012-9880-9

    CAS  PubMed  Google Scholar 

  • Kuhn PH, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, Rossner S, Lichtenthaler SF (2010) ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 29(17):3020–3032. doi:10.1038/emboj.2010.167

    CAS  PubMed Central  PubMed  Google Scholar 

  • LaFerla FM (2010) Pathways linking Abeta and tau pathologies. Biochem Soc Trans 38(4):993–995. doi:10.1042/BST0380993

    CAS  PubMed  Google Scholar 

  • LaFerla FM, Tinkle BT, Bieberich CJ, Haudenschild CC, Jay G (1995) The Alzheimer’s A beta peptide induces neurodegeneration and apoptotic cell death in transgenic mice. Nat Genet 9(1):21–30. doi:10.1038/ng0195-21

    CAS  PubMed  Google Scholar 

  • Lalli MA, Cox HC, Arcila ML, Cadavid L, Moreno S, Garcia G, Madrigal L, Reiman EM, Arcos-Burgos M, Bedoya G, Brunkow ME, Glusman G, Roach JC, Hood L, Kosik KS, Lopera F (2014) Origin of the PSEN1 E280A mutation causing early-onset Alzheimer’s disease. Alzheimers Dement 10(5 Suppl):S277–S283.e10. doi:10.1016/j.jalz.2013.09.005

  • Lambracht-Washington D, Rosenberg RN (2013) Advances in the development of vaccines for Alzheimer’s disease. Discov Med 15(84):319–326

    PubMed Central  PubMed  Google Scholar 

  • Lang M, Fan Q, Wang L, Zheng Y, Xiao G, Wang X, Wang W, Zhong Y, Zhou B (2013) Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer’s disease-like symptoms. Neurobiol Aging 34(11):2604–2612. doi:10.1016/j.neurobiolaging.2013.05.029

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee JH, Cheon YH, Woo RS, Song DY, Moon C, Baik TK (2012) Evidence of early involvement of apoptosis inducing factor-induced neuronal death in Alzheimer brain. Anat Cell Biol 45(1):26–37. doi:10.5115/acb.2012.45.1.26

    PubMed Central  PubMed  Google Scholar 

  • Lee S, Bang SM, Lee JW, Cho KS (2014) Evaluation of traditional medicines for neurodegenerative diseases using Drosophila models. Evid Based Complement Alternat Med 2014:967462. doi:10.1155/2014/967462

    PubMed Central  PubMed  Google Scholar 

  • Lemere CA, Lopera F, Kosik KS, Lendon CL, Ossa J, Saido TC, Yamaguchi H, Ruiz A, Martinez A, Madrigal L, Hincapie L, Arango JC, Anthony DC, Koo EH, Goate AM, Selkoe DJ, Arango JC (1996) The E280A presenilin 1 Alzheimer mutation produces increased A beta 42 deposition and severe cerebellar pathology. Nat Med 2(10):1146–1150

    CAS  PubMed  Google Scholar 

  • Leuner K, Schulz K, Schütt T, Pantel J, Prvulovic D, Rhein V, Savaskan E, Czech C, Eckert A, Müller WE (2012) Peripheral mitochondrial dysfunction in Alzheimer’s disease: focus on lymphocytes. Mol Neurobiol 46(1):194–204. doi:10.1007/s12035-012-8300-y

    CAS  PubMed  Google Scholar 

  • Li YM, Chan HY, Huang Y, Chen ZY (2007) Green tea catechins upregulate superoxide dismutase and catalase in fruit flies. Mol Nutr Food Res 51(5):546–554. doi:10.1002/mnfr.200600238

    CAS  PubMed  Google Scholar 

  • Liao D, Miller EC, Teravskis PJ (2014) Tau acts as a mediator for Alzheimer’s disease-related synaptic deficits. Eur J Neurosci 39(7):1202–1213. doi:10.1111/ejn.12504

    PubMed Central  PubMed  Google Scholar 

  • Liu P, Kong M, Yuan S, Liu J, Wang P (2014) History and experience: a survey of traditional chinese medicine treatment for Alzheimer’s disease. Evid Based Complement Alternat Med 2014:642128. doi:10.1155/2014/642128

    PubMed Central  PubMed  Google Scholar 

  • Londono AC, Castellanos FX, Arbelaez A, Ruiz A, Aguirre-Acevedo DC, Richardson AM, Easteal S, Lidbury BA, Arcos-Burgos M, Lopera F (2013) An (1)H-MRS framework predicts the onset of Alzheimer’s disease symptoms in PSEN1 mutation carriers. Alzheimers Dement. doi:10.1016/j.jalz.2013.08.282

    PubMed  Google Scholar 

  • Lopera A, Arcos M, Madrigal L, Kosik K, Cornejo W, Ossa J (1994) Alzheimer type presenile dementia with familial aggregation in Antioquia, Colombia. Acta Neurol Col 10:173–187

    Google Scholar 

  • Lopera F, Ardilla A, Martínez A, Madrigal L, Arango-Viana JC, Lemere CA, Arango-Lasprilla JC, Hincapíe L, Arcos-Burgos M, Ossa JE, Behrens IM, Norton J, Lendon C, Goate AM, Ruiz-Linares A, Rosselli M, Kosik KS (1997) Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA 277(10):793–799

    CAS  PubMed  Google Scholar 

  • Luo L, Tully T, White K (1992) Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene. Neuron 9(4):595–605

    CAS  PubMed  Google Scholar 

  • Mandel SA, Amit T, Kalfon L, Reznichenko L, Weinreb O, Youdim MB (2008) Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG). J Alzheimers Dis 15(2):211–222

    CAS  PubMed  Google Scholar 

  • Mao Z, Davis RL (2009) Eight different types of dopaminergic neurons innervate the Drosophila mushroom body neuropil: anatomical and physiological heterogeneity. Front Neural Circuits 3:5. doi:10.3389/neuro.04.005.2009

    PubMed Central  PubMed  Google Scholar 

  • Marinho HS, Real C, Cyrne L, Soares H, Antunes F (2014) Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox Biol 2:535–562. doi:10.1016/j.redox.2014.02.006

    CAS  PubMed Central  PubMed  Google Scholar 

  • Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23(1):134–147

    CAS  PubMed  Google Scholar 

  • Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82(12):4245–4249

    CAS  PubMed Central  PubMed  Google Scholar 

  • McLellan ME, Kajdasz ST, Hyman BT, Bacskai BJ (2003) In vivo imaging of reactive oxygen species specifically associated with thioflavine S-positive amyloid plaques by multiphoton microscopy. J Neurosci 23(6):2212–2217

    CAS  PubMed  Google Scholar 

  • Mhatre SD, Satyasi V, Killen M, Paddock BE, Moir RD, Saunders AJ, Marenda DR (2014) Synaptic abnormalities in a Drosophila model of Alzheimer’s disease. Dis Model Mech 7(3):373–385. doi:10.1242/dmm.012104

    PubMed Central  PubMed  Google Scholar 

  • Mirinics ZK, Calafat J, Udby L, Lovelock J, Kjeldsen L, Rothermund K, Sisodia SS, Borregaard N, Corey SJ (2002) Identification of the presenilins in hematopoietic cells with localization of presenilin 1 to neutrophil and platelet granules. Blood Cells Mol Dis 28(1):28–38

    PubMed  Google Scholar 

  • Morales I, Guzmán-Martínez L, Cerda-Troncoso C, Farías GA, Maccioni RB (2014) Neuroinflammation in the pathogenesis of Alzheimer’s disease. A rational framework for the search of novel therapeutic approaches. Front Cell Neurosci 8:112. doi:10.3389/fncel.2014.00112

    PubMed Central  PubMed  Google Scholar 

  • Mori T, Rezai-Zadeh K, Koyama N, Arendash GW, Yamaguchi H, Kakuda N, Horikoshi-Sakuraba Y, Tan J, Town T (2012) Tannic acid is a natural β-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. J Biol Chem 287(9):6912–6927. doi:10.1074/jbc.M111.294025

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mori T, Koyama N, Guillot-Sestier MV, Tan J, Town T (2013) Ferulic acid is a nutraceutical β-secretase modulator that improves behavioral impairment and alzheimer-like pathology in transgenic mice. PLoS One 8(2), e55774. doi:10.1371/journal.pone.0055774

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mourtas S, Lazar AN, Markoutsa E, Duyckaerts C, Antimisiaris SG (2014) Multifunctional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer disease. Eur J Med Chem 80:175–183. doi:10.1016/j.ejmech.2014.04.050

    CAS  PubMed  Google Scholar 

  • Mucke L, Selkoe DJ (2012) Neurotoxicity of amyloid β-protein: synaptic and network dysfunction. Cold Spring Harb Perspect Med 2(7):a006338. doi:10.1101/cshperspect.a006338

    PubMed Central  PubMed  Google Scholar 

  • Mullane K, Williams M (2013) Alzheimer’s therapeutics: continued clinical failures question the validity of the amyloid hypothesis-but what lies beyond? Biochem Pharmacol 85(3):289–305. doi:10.1016/j.bcp.2012.11.014

    CAS  PubMed  Google Scholar 

  • Müller U, Winter P, Graeber MB (2013) A presenilin 1 mutation in the first case of Alzheimer’s disease. Lancet Neurol 12(2):129–130. doi:10.1016/S1474-4422(12)70307-1

    PubMed  Google Scholar 

  • Ng CF, Ko CH, Koon CM, Xian JW, Leung PC, Fung KP, Chan HY, Lau CB (2013) The aqueous extract of rhizome of gastrodia elata protected drosophila and PC12 cells against beta-amyloid-induced neurotoxicity. Evid Based Complement Alternat Med 2013:516741. doi:10.1155/2013/516741

    PubMed Central  PubMed  Google Scholar 

  • Nimmrich V, Ebert U (2009) Is Alzheimer’s disease a result of presynaptic failure? Synaptic dysfunctions induced by oligomeric beta-amyloid. Rev Neurosci 20(1):1–12

    CAS  PubMed  Google Scholar 

  • Norberg E, Orrenius S, Zhivotovsky B (2010) Mitochondrial regulation of cell death: processing of apoptosis-inducing factor (AIF). Biochem Biophys Res Commun 396(1):95–100. doi:10.1016/j.bbrc.2010.02.163

    CAS  PubMed  Google Scholar 

  • Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767

    CAS  PubMed  Google Scholar 

  • Oddo S, Caccamo A, Kitazawa M, Tseng BP, LaFerla FM (2003) Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer’s disease. Neurobiol Aging 24(8):1063–1070

    CAS  PubMed  Google Scholar 

  • Ofstad TA, Zuker CS, Reiser MB (2011) Visual place learning in Drosophila melanogaster. Nature 474(7350):204–207. doi:10.1038/nature10131

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oleinik NV, Krupenko NI, Krupenko SA (2007) Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene 26(51):7222–7230. doi:10.1038/sj.onc.1210526

    CAS  PubMed  Google Scholar 

  • Olovnikov IA, Kravchenko JE, Chumakov PM (2009) Homeostatic functions of the p53 tumor suppressor: regulation of energy metabolism and antioxidant defense. Semin Cancer Biol 19(1):32–41. doi:10.1016/j.semcancer.2008.11.005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ono K, Li L, Takamura Y, Yoshiike Y, Zhu L, Han F, Mao X, Ikeda T, Takasaki J, Nishijo H, Takashima A, Teplow DB, Zagorski MG, Yamada M (2012) Phenolic compounds prevent amyloid β-protein oligomerization and synaptic dysfunction by site-specific binding. J Biol Chem 287(18):14631–14643. doi:10.1074/jbc.M111.325456

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oortveld MA, Keerthikumar S, Oti M, Nijhof B, Fernandes AC, Kochinke K, Castells-Nobau A, van Engelen E, Ellenkamp T, Eshuis L, Galy A, van Bokhoven H, Habermann B, Brunner HG, Zweier C, Verstreken P, Huynen MA, Schenck A (2013) Human intellectual disability genes form conserved functional modules in Drosophila. PLoS Genet 9(10), e1003911. doi:10.1371/journal.pgen.1003911

    PubMed Central  PubMed  Google Scholar 

  • Orlando RA, Gonzales AM, Royer RE, Deck LM, Vander Jagt DL (2012) A chemical analog of curcumin as an improved inhibitor of amyloid Abeta oligomerization. PLoS One 7(3), e31869. doi:10.1371/journal.pone.0031869

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C (2011) Life span and locomotor activity modification by glucose and polyphenols in Drosophila melanogaster chronically exposed to oxidative stress-stimuli: implications in Parkinson’s disease. Neurochem Res 36(6):1073–1086. doi:10.1007/s11064-011-0451-0

    CAS  PubMed  Google Scholar 

  • Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C (2013) Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson’s disease model. Genet Mol Biol 36(4):608–615. doi:10.1590/S1415-47572013000400020

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pagani L, Eckert A (2011) Amyloid-Beta interaction with mitochondria. Int J Alzheimers Dis 2011:925050. doi:10.4061/2011/925050

    PubMed Central  PubMed  Google Scholar 

  • Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci 13(7):812–818. doi:10.1038/nn.2583

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pandey UB, Nichols CD (2011) Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol Rev 63(2):411–436. doi:10.1124/pr.110.003293

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park SH, Lee S, Hong YK, Hwang S, Lee JH, Bang SM, Kim YK, Koo BS, Lee IS, Cho KS (2013) Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer’s disease. Biol Pharm Bull 36(3):390–398

    CAS  PubMed  Google Scholar 

  • Parodi J, Sepúlveda FJ, Roa J, Opazo C, Inestrosa NC, Aguayo LG (2010) Beta-amyloid causes depletion of synaptic vesicles leading to neurotransmission failure. J Biol Chem 285(4):2506–2514. doi:10.1074/jbc.M109.030023

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perisse E, Burke C, Huetteroth W, Waddell S (2013a) Shocking revelations and saccharin sweetness in the study of Drosophila olfactory memory. Curr Biol 23(17):R752–R763. doi:10.1016/j.cub.2013.07.060

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perisse E, Yin Y, Lin AC, Lin S, Huetteroth W, Waddell S (2013b) Different kenyon cell populations drive learned approach and avoidance in Drosophila. Neuron 79(5):945–956. doi:10.1016/j.neuron.2013.07.045

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perron NR, Brumaghim JL (2009) A review of the antioxidant mechanisms of polyphenol compounds related to iron binding. Cell Biochem Biophys 53(2):75–100. doi:10.1007/s12013-009-9043-x

    CAS  PubMed  Google Scholar 

  • Perron NR, Wang HC, Deguire SN, Jenkins M, Lawson M, Brumaghim JL (2010) Kinetics of iron oxidation upon polyphenol binding. Dalton Trans 39(41):9982–9987. doi:10.1039/c0dt00752h

    CAS  PubMed  Google Scholar 

  • Persson T, Popescu BO, Cedazo-Minguez A (2014) Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid Med Cell Longev 2014:427318. doi:10.1155/2014/427318

    PubMed Central  PubMed  Google Scholar 

  • Pfleger CM, Wang J, Friedman L, Vittorino R, Conley LM, Ho L, Fivecoat HC, Pasinetti GM (2010) Grape-seed polyphenolic extract improves the eye phenotype in a Drosophila model of tauopathy. Int J Alzheimers Dis. doi:10.4061/2010/576357

    PubMed Central  PubMed  Google Scholar 

  • Phelps CB, Brand AH (1998) Ectopic gene expression in Drosophila using GAL4 system. Methods 14(4):367–379. doi:10.1006/meth.1998.0592

    CAS  PubMed  Google Scholar 

  • Pitman JL, DasGupta S, Krashes MJ, Leung B, Perrat PN, Waddell S (2009) There are many ways to train a fly. Fly (Austin) 3(1):3–9

    Google Scholar 

  • Ploia C, Antoniou X, Sclip A, Grande V, Cardinetti D, Colombo A, Canu N, Benussi L, Ghidoni R, Forloni G, Borsello T (2011) JNK plays a key role in tau hyperphosphorylation in Alzheimer’s disease models. J Alzheimers Dis 26(2):315–329. doi:10.3233/JAD-2011-110320

    CAS  PubMed  Google Scholar 

  • Porat Y, Abramowitz A, Gazit E (2006) Inhibition of amyloid fibril formation by polyphenols: structural similarity and aromatic interactions as a common inhibition mechanism. Chem Biol Drug Des 67(1):27–37. doi:10.1111/j.1747-0285.2005.00318.x

    CAS  PubMed  Google Scholar 

  • Praticò D (2008) Evidence of oxidative stress in Alzheimer’s disease brain and antioxidant therapy: lights and shadows. Ann N Y Acad Sci 1147:70–78. doi:10.1196/annals.1427.010

    PubMed  Google Scholar 

  • Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP (2013) The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement 9(1):63–75.e62. doi:10.1016/j.jalz.2012.11.007

    PubMed  Google Scholar 

  • Prüßing K, Voigt A, Schulz JB (2013) Drosophila melanogaster as a model organism for Alzheimer’s disease. Mol Neurodegener 8:35. doi:10.1186/1750-1326-8-35

    PubMed Central  PubMed  Google Scholar 

  • Quiroz YT, Stern CE, Reiman EM, Brickhouse M, Ruiz A, Sperling RA, Lopera F, Dickerson BC (2013) Cortical atrophy in presymptomatic Alzheimer’s disease presenilin 1 mutation carriers. J Neurol Neurosurg Psychiatry 84(5):556–561. doi:10.1136/jnnp-2012-303299

    PubMed Central  PubMed  Google Scholar 

  • Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545(1):51–64. doi:10.1016/j.ejphar.2006.06.025

    CAS  PubMed  Google Scholar 

  • Ramirez-Bermudez J (2012) Alzheimer’s disease: critical notes on the history of a medical concept. Arch Med Res 43(8):595–599. doi:10.1016/j.arcmed.2012.11.008

    PubMed  Google Scholar 

  • Ran Y, Cruz PE, Ladd TB, Fauq AH, Jung JI, Matthews J, Felsenstein KM, Golde TE (2014) γ-Secretase processing and effects of γ-secretase inhibitors and modulators on long Aβ peptides in cells. J Biol Chem 289(6):3276–3287. doi:10.1074/jbc.M113.512921

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reiman EM, Langbaum JB, Fleisher AS, Caselli RJ, Chen K, Ayutyanont N, Quiroz YT, Kosik KS, Lopera F, Tariot PN (2011) Alzheimer’s prevention initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis 26(Suppl 3):321–329. doi:10.3233/JAD-2011-0059

    PubMed Central  PubMed  Google Scholar 

  • Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, Fagan AM, Shah AR, Alvarez S, Arbelaez A, Giraldo M, Acosta-Baena N, Sperling RA, Dickerson B, Stern CE, Tirado V, Munoz C, Reiman RA, Huentelman MJ, Alexander GE, Langbaum JB, Kosik KS, Tariot PN, Lopera F (2012) Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer’s disease in the presenilin 1 E280A kindred: a case–control study. Lancet Neurol 11(12):1048–1056

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reynolds CH, Utton MA, Gibb GM, Yates A, Anderton BH (1997) Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau protein. J Neurochem 68(4):1736–1744

    CAS  PubMed  Google Scholar 

  • Rice-Evans C, Miller N, Paganga G (1997) Antioxidant properties of phenolic compounds. Trends Plant Sci 2(4):152–159

    Google Scholar 

  • Rio MJ, Velez-Pardo C (2008) Paraquat induces apoptosis in human lymphocytes: protective and rescue effects of glucose, cannabinoids and insulin-like growth factor-1. Growth Factors 26(1):49–60. doi:10.1080/08977190801984205

    PubMed  Google Scholar 

  • Rival T, Page RM, Chandraratna DS, Sendall TJ, Ryder E, Liu B, Lewis H, Rosahl T, Hider R, Camargo LM, Shearman MS, Crowther DC, Lomas DA (2009) Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer’s disease. Eur J Neurosci 29(7):1335–1347. doi:10.1111/j.1460-9568.2009.06701.x

    PubMed Central  PubMed  Google Scholar 

  • Rivière C, Richard T, Quentin L, Krisa S, Mérillon JM, Monti JP (2007) Inhibitory activity of stilbenes on Alzheimer’s beta-amyloid fibrils in vitro. Bioorg Med Chem 15(2):1160–1167. doi:10.1016/j.bmc.2006.09.069

    PubMed  Google Scholar 

  • Rivière C, Papastamoulis Y, Fortin PY, Delchier N, Andriamanarivo S, Waffo-Teguo P, Kapche GD, Amira-Guebalia H, Delaunay JC, Mérillon JM, Richard T, Monti JP (2010) New stilbene dimers against amyloid fibril formation. Bioorg Med Chem Lett 20(11):3441–3443. doi:10.1016/j.bmcl.2009.09.074

    PubMed  Google Scholar 

  • Rooke J, Pan D, Xu T, Rubin GM (1996) KUZ, a conserved metalloprotease-disintegrin protein with two roles in Drosophila neurogenesis. Science 273(5279):1227–1231

    CAS  PubMed  Google Scholar 

  • Rosen DR, Martin-Morris L, Luo LQ, White K (1989) A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. Proc Natl Acad Sci U S A 86(7):2478–2482

    CAS  PubMed Central  PubMed  Google Scholar 

  • Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17(9):2596–2606. doi:10.1093/emboj/17.9.2596

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sato T, Dohmae N, Qi Y, Kakuda N, Misonou H, Mitsumori R, Maruyama H, Koo EH, Haass C, Takio K, Morishima-Kawashima M, Ishiura S, Ihara Y (2003) Potential link between amyloid beta-protein 42 and C-terminal fragment gamma 49–99 of beta-amyloid precursor protein. J Biol Chem 278(27):24294–24301. doi:10.1074/jbc.M211161200

    CAS  PubMed  Google Scholar 

  • Sato M, Murakami K, Uno M, Nakagawa Y, Katayama S, Akagi K, Masuda Y, Takegoshi K, Irie K (2013) Site-specific inhibitory mechanism for amyloid β42 aggregation by catechol-type flavonoids targeting the Lys residues. J Biol Chem 288(32):23212–23224. doi:10.1074/jbc.M113.464222

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T, Hu K, Huang J, Johnson-Wood K, Khan K, Kholodenko D, Lee M, Liao Z, Lieberburg I, Motter R, Mutter L, Soriano F, Shopp G, Vasquez N, Vandevert C, Walker S, Wogulis M, Yednock T, Games D, Seubert P (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400(6740):173–177. doi:10.1038/22124

    CAS  PubMed  Google Scholar 

  • Schoonbroodt S, Ferreira V, Best-Belpomme M, Boelaert JR, Legrand-Poels S, Korner M, Piette J (2000) Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of I kappa B alpha in NF-kappa B activation by an oxidative stress. J Immunol 164(8):4292–4300

    CAS  PubMed  Google Scholar 

  • Schottyky J (1932) Uber prasenile verblodungen. Z Gesamte Neurol Psychiat 140:333–387

    Google Scholar 

  • Selznick LA, Holtzman DM, Han BH, Gökden M, Srinivasan AN, Johnson EM, Roth KA (1999) In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease. J Neuropathol Exp Neurol 58(9):1020–1026

    CAS  PubMed  Google Scholar 

  • Sepúlveda FJ, Fierro H, Fernandez E, Castillo C, Peoples RW, Opazo C, Aguayo LG (2014) Nature of the neurotoxic membrane actions of amyloid-β on hippocampal neurons in Alzheimer’s disease. Neurobiol Aging 35(3):472–481. doi:10.1016/j.neurobiolaging.2013.08.035

    PubMed  Google Scholar 

  • Sepulveda-Falla D, Glatzel M, Lopera F (2012) Phenotypic profile of early-onset familial Alzheimer’s disease caused by presenilin-1 E280A mutation. J Alzheimers Dis 32(1):1–12. doi:10.3233/JAD-2012-120907

    CAS  PubMed  Google Scholar 

  • Sharma AK, Pavlova ST, Kim J, Finkelstein D, Hawco NJ, Rath NP, Mirica LM (2012) Bifunctional compounds for controlling metal-mediated aggregation of the aβ42 peptide. J Am Chem Soc 134(15):6625–6636. doi:10.1021/ja210588m

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sharoar MG, Thapa A, Shahnawaz M, Ramasamy VS, Woo ER, Shin SY, Park IS (2012) Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates. J Biomed Sci 19:104. doi:10.1186/1423-0127-19-104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375(6534):754–760. doi:10.1038/375754a0

    CAS  PubMed  Google Scholar 

  • Shoji M, Iwakami N, Takeuchi S, Waragai M, Suzuki M, Kanazawa I, Lippa CF, Ono S, Okazawa H (2000) JNK activation is associated with intracellular beta-amyloid accumulation. Brain Res Mol Brain Res 85(1–2):221–233

    CAS  PubMed  Google Scholar 

  • Silva AJ, Murphy GG (1999) cAMP and memory: a seminal lesson from Drosophila and Aplysia. Brain Res Bull 50(5–6):441–442

    CAS  PubMed  Google Scholar 

  • Sitaraman D, LaFerriere H, Birman S, Zars T (2012) Serotonin is critical for rewarded olfactory short-term memory in Drosophila. J Neurogenet 26(2):238–244. doi:10.3109/01677063.2012.666298

    CAS  PubMed  Google Scholar 

  • Skoulakis EM, Grammenoudi S (2006) Dunces and da Vincis: the genetics of learning and memory in Drosophila. Cell Mol Life Sci 63(9):975–988. doi:10.1007/s00018-006-6023-9

    CAS  PubMed  Google Scholar 

  • Smith DG, Cappai R, Barnham KJ (2007) The redox chemistry of the Alzheimer’s disease amyloid beta peptide. Biochim Biophys Acta 1768(8):1976–1990. doi:10.1016/j.bbamem.2007.02.002

    CAS  PubMed  Google Scholar 

  • Song J, Wang S, Tan M, Jia J (2012) G1/S checkpoint proteins in peripheral blood lymphocytes are potentially diagnostic biomarkers for Alzheimer’s disease. Neurosci Lett 526(2):144–149. doi:10.1016/j.neulet.2012.08.020

    CAS  PubMed  Google Scholar 

  • Soobrattee MA, Neergheen VS, Luximon-Ramma A, Aruoma OI, Bahorun T (2005) Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res 579(1–2):200–213. doi:10.1016/j.mrfmmm.2005.03.023

    CAS  PubMed  Google Scholar 

  • Spuch C, Ortolano S, Navarro C (2012) New insights in the amyloid-Beta interaction with mitochondria. J Aging Res 2012:324968. doi:10.1155/2012/324968

    PubMed Central  PubMed  Google Scholar 

  • Squitti R (2012) Metals in Alzheimer’s disease: a systemic perspective. Front Biosci (Landmark Ed) 17:451–472

    CAS  Google Scholar 

  • Sroka Z, Cisowski W (2003) Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acids. Food Chem Toxicol 41(6):753–758

    CAS  PubMed  Google Scholar 

  • Stelzmann RA, Alzheimer A, Schnitzlein HN, Murtagh FR (1995) An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde”. Clin Anat 8(6):429–431. doi:10.1002/ca.980080612

  • Stempfle D, Kanwar R, Loewer A, Fortini ME, Merdes G (2010) In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity. Mol Cell Biol 30(13):3165–3175. doi:10.1128/MCB.00030-10

    CAS  PubMed Central  PubMed  Google Scholar 

  • Su JH, Zhao M, Anderson AJ, Srinivasan A, Cotman CW (2001) Activated caspase-3 expression in Alzheimer’s and aged control brain: correlation with Alzheimer pathology. Brain Res 898(2):350–357

    CAS  PubMed  Google Scholar 

  • Sultana R, Baglioni M, Cecchetti R, Cai J, Klein JB, Bastiani P, Ruggiero C, Mecocci P, Butterfield DA (2013) Lymphocyte mitochondria: toward identification of peripheral biomarkers in the progression of Alzheimer disease. Free Radic Biol Med 65:595–606. doi:10.1016/j.freeradbiomed.2013.08.001

    CAS  PubMed  Google Scholar 

  • Tabner BJ, El-Agnaf OM, Turnbull S, German MJ, Paleologou KE, Hayashi Y, Cooper LJ, Fullwood NJ, Allsop D (2005) Hydrogen peroxide is generated during the very early stages of aggregation of the amyloid peptides implicated in Alzheimer disease and familial British dementia. J Biol Chem 280(43):35789–35792. doi:10.1074/jbc.C500238200

    CAS  PubMed  Google Scholar 

  • Takahashi N, Kariya S, Hirano M, Ueno S (2003) Two novel spliced presenilin 2 transcripts in human lymphocyte with oxidant stress and brain. Mol Cell Biochem 252(1–2):279–283

    CAS  PubMed  Google Scholar 

  • Takahashi RH, Capetillo-Zarate E, Lin MT, Milner TA, Gouras GK (2010) Co-occurrence of Alzheimer’s disease ß-amyloid and τ pathologies at synapses. Neurobiol Aging 31(7):1145–1152. doi:10.1016/j.neurobiolaging.2008.07.021

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takahashi RH, Capetillo-Zarate E, Lin MT, Milner TA, Gouras GK (2013) Accumulation of intraneuronal β-amyloid 42 peptides is associated with early changes in microtubule-associated protein 2 in neurites and synapses. PLoS One 8(1), e51965. doi:10.1371/journal.pone.0051965

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tapson VF, Boni-Schnetzler M, Pilch PF, Center DM, Berman JS (1988) Structural and functional characterization of the human T lymphocyte receptor for insulin-like growth factor I in vitro. J Clin Invest 82(3):950–957. doi:10.1172/JCI113703

    Google Scholar 

  • Tare M, Modi RM, Nainaparampil JJ, Puli OR, Bedi S, Fernandez-Funez P, Kango-Singh M, Singh A (2011) Activation of JNK signaling mediates amyloid-ß-dependent cell death. PLoS One 6(9), e24361. doi:10.1371/journal.pone.0024361

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thakur A, Wang X, Siedlak SL, Perry G, Smith MA, Zhu X (2007) c-Jun phosphorylation in Alzheimer disease. J Neurosci Res 85(8):1668–1673. doi:10.1002/jnr.21298

    CAS  PubMed  Google Scholar 

  • Tharp WG, Sarkar IN (2013) Origins of amyloid-β. BMC Genomics 14:290. doi:10.1186/1471-2164-14-290

    CAS  PubMed Central  PubMed  Google Scholar 

  • Thies W, Bleiler L, Association As (2013) 2013 Alzheimer’s disease facts and figures. Alzheimers Dement 9(2):208–245. doi:10.1016/j.jalz.2013.02.003

    Google Scholar 

  • Troy CM, Rabacchi SA, Xu Z, Maroney AC, Connors TJ, Shelanski ML, Greene LA (2001) beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation. J Neurochem 77(1):157–164

    CAS  PubMed  Google Scholar 

  • Tsimogiannis D, Oreopoulou V (2004) Free radical scavenging and antioxidant activity of 5,7,3’,4’-hydroxy-substituted flavonoids. Innov Food Sci Emerging Technol 5:523–528

    CAS  Google Scholar 

  • Tsimogiannis D, Oreopoulou V (2006) The contribution of flavonoid C-ring on the DPPH free radical scavenging efficiency. A kinetic approach for the 3’,4’-hydroxy substituted members. Innov Food Sci Emmerging Technol 7:140–146

    CAS  Google Scholar 

  • Unicesi (2013) Boletin de prensa #229. Accessed 1 Aug 2014

    Google Scholar 

  • Urano T, Tohda C (2010) Icariin improves memory impairment in Alzheimer’s disease model mice (5xFAD) and attenuates amyloid β-induced neurite atrophy. Phytother Res 24(11):1658–1663. doi:10.1002/ptr.3183

    CAS  PubMed  Google Scholar 

  • van der Voet M, Nijhof B, Oortveld MA, Schenck A (2014) Drosophila models of early onset cognitive disorders and their clinical applications. Neurosci Biobehav Rev. doi:10.1016/j.neubiorev.2014.01.013

    PubMed  Google Scholar 

  • Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286(5440):735–741

    CAS  PubMed  Google Scholar 

  • Vauzour D (2014) Effect of flavonoids on learning, memory and neurocognitive performance: relevance and potential implications for Alzheimer’s disease pathophysiology. J Sci Food Agric 94(6):1042–1056. doi:10.1002/jsfa.6473

    CAS  PubMed  Google Scholar 

  • Velez-Pardo C, Del Rio MJ (2006) Avoidance of Abeta[(25–35)]/(H(2)O(2))-induced apoptosis in lymphocytes by the cannabinoid agonists CP55,940 and JWH-015 via receptor-independent and PI3K-dependent mechanisms: role of NF-kappaB and p53. Med Chem 2(5):471–479

    CAS  PubMed  Google Scholar 

  • Velez-Pardo C, Ospina GG, Jimenez del Rio M (2002) Abeta[25–35] peptide and iron promote apoptosis in lymphocytes by an oxidative stress mechanism: involvement of H2O2, caspase-3, NF-kappaB, p53 and c-Jun. Neurotoxicology 23(3):351–365

    CAS  PubMed  Google Scholar 

  • Velez-Pardo C, Arellano JI, Cardona-Gomez P, Jimenez Del Rio M, Lopera F, De Felipe J (2004) CA1 hippocampal neuronal loss in familial Alzheimer’s disease presenilin-1 E280A mutation is related to epilepsy. Epilepsia 45(7):751–756. doi:10.1111/j.0013-9580.2004.55403.x

    CAS  PubMed  Google Scholar 

  • Villaño D, Fernández-Pachón MS, Moyá ML, Troncoso AM, García-Parrilla MC (2007) Radical scavenging ability of polyphenolic compounds towards DPPH free radical. Talanta 71(1):230–235. doi:10.1016/j.talanta.2006.03.050

    PubMed  Google Scholar 

  • Viña J, Lloret A, Giraldo E, Badia MC, Alonso MD (2011) Antioxidant pathways in Alzheimer’s disease: possibilities of intervention. Curr Pharm Des 17(35):3861–3864

    PubMed  Google Scholar 

  • Waddell S (2010) Dopamine reveals neural circuit mechanisms of fly memory. Trends Neurosci 33(10):457–464. doi:10.1016/j.tins.2010.07.001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang X, Kim JR, Lee SB, Kim YJ, Jung MY, Kwon HW, Ahn YJ (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. doi:10.1186/1472-6882-14-88

    PubMed Central  PubMed  Google Scholar 

  • Weinreb O, Mandel S, Amit T, Youdim MB (2004) Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J Nutr Biochem 15(9):506–516. doi:10.1016/j.jnutbio.2004.05.002

    CAS  PubMed  Google Scholar 

  • Weuve J, Hebert LE, Scherr PA, Evans DA (2014) Deaths in the United States among persons with Alzheimer’s disease (2010–2050). Alzheimers Dement 10(2):e40–e46. doi:10.1016/j.jalz.2014.01.004

    PubMed Central  PubMed  Google Scholar 

  • Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398(6727):513–517. doi:10.1038/19077

    CAS  PubMed  Google Scholar 

  • Yanagisawa D, Taguchi H, Yamamoto A, Shirai N, Hirao K, Tooyama I (2011) Curcuminoid binds to amyloid-β1-42 oligomer and fibril. J Alzheimers Dis 24(Suppl 2):33–42. doi:10.3233/JAD-2011-102100

    CAS  PubMed  Google Scholar 

  • Yang D, Tournier C, Wysk M, Lu HT, Xu J, Davis RJ, Flavell RA (1997) Targeted disruption of the MKK4 gene causes embryonic death, inhibition of c-Jun NH2-terminal kinase activation, and defects in AP-1 transcriptional activity. Proc Natl Acad Sci U S A 94(7):3004–3009

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu Y, Xie ZL, Gao H, Ma WW, Dai Y, Wang Y, Zhong Y, Yao XS (2009) Bioactive iridoid glucosides from the fruit of Gardenia jasminoides. J Nat Prod 72(8):1459–1464. doi:10.1021/np900176q

    CAS  PubMed  Google Scholar 

  • Yu W, Mechawar N, Krantic S, Quirion R (2010) Evidence for the involvement of apoptosis-inducing factor-mediated caspase-independent neuronal death in Alzheimer disease. Am J Pathol 176(5):2209–2218. doi:10.2353/ajpath.2010.090496

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu Y, Feng XL, Gao H, Xie ZL, Dai Y, Huang XJ, Kurihara H, Ye WC, Zhong Y, Yao XS (2012) Chemical constituents from the fruits of Gardenia jasminoides Ellis. Fitoterapia 83(3):563–567. doi:10.1016/j.fitote.2011.12.027

    CAS  PubMed  Google Scholar 

  • Zhao M, Su J, Head E, Cotman CW (2003) Accumulation of caspase cleaved amyloid precursor protein represents an early neurodegenerative event in aging and in Alzheimer’s disease. Neurobiol Dis 14(3):391–403

    CAS  PubMed  Google Scholar 

  • Zou H, Li Y, Liu X, Wang X (1999) An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274(17):11549–11556

    CAS  PubMed  Google Scholar 

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Acknowledgements

The work was supported by “Comité para el Desarrollo de la Investigación”, CODI-UdeA (Grant #EO1617 to MJimenez-Del-Rio). We thank Ortega-Arellano H for assistance with Fig. 2.4 and Table (Learning and memory, apoptosis) data, and Bonilla-Ramirez L for assistance with Table (APP, metal metabolism) data.

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Jimenez-Del-Rio, M., Velez-Pardo, C. (2015). Alzheimer’s Disease, Drosophila melanogaster and Polyphenols. In: Vassallo, N. (eds) Natural Compounds as Therapeutic Agents for Amyloidogenic Diseases. Advances in Experimental Medicine and Biology, vol 863. Springer, Cham. https://doi.org/10.1007/978-3-319-18365-7_2

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