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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
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
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
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
Aisen PS (2009) Alzheimer’s disease therapeutic research: the path forward. Alzheimers Res Ther 1(1):2. doi:10.1186/alzrt2
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
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
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
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
Arcos-Burgos M, Muenke M (2002) Genetics of population isolates. Clin Genet 61(4):233–247
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
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
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
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
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
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
Behl C, Davis JB, Lesley R, Schubert D (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77(6):817–827
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
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
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
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
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
Boutajangout A, Wisniewski T (2014) Tau-based therapeutic approaches for Alzheimer’s disease – a mini-review. Gerontology. doi:10.1159/000358875
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
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
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
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
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
Campbell RA, Turner GC (2010) The mushroom body. Curr Biol 20(1):R11–R12. doi:10.1016/j.cub.2009.10.031
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
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
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
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
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
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
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
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
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
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
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
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
De Strooper B (2003) Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 38(1):9–12
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
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
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
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
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
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
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
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
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
Fargo K, Bleiler L (2014) Alzheimer’s Association report. Alzheimers Dement 10(2):e47–e92
Fettelschoss A, Zabel F, Bachmann MF (2014) Vaccination against Alzheimer disease: an update on future strategies. Hum Vaccin Immunother 10(4)
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
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
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
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
Frank DA, Greenberg ME (1994) CREB: a mediator of long-term memory from mollusks to mammals. Cell 79(1):5–8
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
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
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
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
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
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
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
Ghosh AK, Osswald HL (2014) BACE1 (β-secretase) inhibitors for the treatment of Alzheimer’s disease. Chem Soc Rev. doi:10.1039/c3cs60460h
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Hardy J (2006) Has the amyloid cascade hypothesis for Alzheimer’s disease been proved? Curr Alzheimer Res 3(1):71–73
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
Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256(5054):184–185
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
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
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
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
Hider RC, Liu ZD, Khodr HH (2001) Metal chelation of polyphenols. Methods Enzymol 335:190–203
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Kim HG, Oh MS (2012) Herbal medicines for the prevention and treatment of Alzheimer’s disease. Curr Pharm Des 18(1):57–75
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
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
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
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
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
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
Korczyn AD (2008) The amyloid cascade hypothesis. Alzheimers Dement 4(3):176–178. doi:10.1016/j.jalz.2007.11.008
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
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
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
LaFerla FM (2010) Pathways linking Abeta and tau pathologies. Biochem Soc Trans 38(4):993–995. doi:10.1042/BST0380993
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Markesbery WR (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23(1):134–147
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Ofstad TA, Zuker CS, Reiser MB (2011) Visual place learning in Drosophila melanogaster. Nature 474(7350):204–207. doi:10.1038/nature10131
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
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
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
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
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
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
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
Pagani L, Eckert A (2011) Amyloid-Beta interaction with mitochondria. Int J Alzheimers Dis 2011:925050. doi:10.4061/2011/925050
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
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
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
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
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
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
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
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
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
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
Phelps CB, Brand AH (1998) Ectopic gene expression in Drosophila using GAL4 system. Methods 14(4):367–379. doi:10.1006/meth.1998.0592
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
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
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
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
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
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
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
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
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
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
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
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
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
Rice-Evans C, Miller N, Paganga G (1997) Antioxidant properties of phenolic compounds. Trends Plant Sci 2(4):152–159
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
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
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
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
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
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
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
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
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
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
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
Schottyky J (1932) Uber prasenile verblodungen. Z Gesamte Neurol Psychiat 140:333–387
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
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
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
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
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
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
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
Silva AJ, Murphy GG (1999) cAMP and memory: a seminal lesson from Drosophila and Aplysia. Brain Res Bull 50(5–6):441–442
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
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
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
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
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
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
Squitti R (2012) Metals in Alzheimer’s disease: a systemic perspective. Front Biosci (Landmark Ed) 17:451–472
Sroka Z, Cisowski W (2003) Hydrogen peroxide scavenging, antioxidant and anti-radical activity of some phenolic acids. Food Chem Toxicol 41(6):753–758
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
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
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
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
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
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
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
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
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
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
Tharp WG, Sarkar IN (2013) Origins of amyloid-β. BMC Genomics 14:290. doi:10.1186/1471-2164-14-290
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
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
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
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
Unicesi (2013) Boletin de prensa #229. Accessed 1 Aug 2014
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
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
Download citation
DOI: https://doi.org/10.1007/978-3-319-18365-7_2
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-18364-0
Online ISBN: 978-3-319-18365-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)