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Amyloid-β Production: Major Link Between Oxidative Stress and BACE1

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Abstract

Sequential endoproteolytic cleavages operated by the γ-secretase and the β-secretase (BACE1) on the β-amyloid precursor protein result in the production of the β-amyloid (Aβ) species, with two C-terminal variants, at residue 40 or at residue 42. Accumulation in brain tissue of aggregates of Aβ42 is the major pathogenetic event in Alzheimer’s disease (AD). The causes of Aβ accumulation in the common sporadic form of AD are not completely understood, but they are likely to include oxidative stress (OS). Data reviewed here shed light on how Aβ generation, oxidative stress, and secretase functions are intimately related in sporadic AD. According to our hypothesis, in sporadic AD, OS resulted from several cellular insults such as aging, hypoxia, hyperglycemia, and hypercholesterolemia—that are well-known risk factors for AD development—can determine a primary induction of γ-secretase and BACE1. The loop proceeds with the generation of Aβ42 and its signaling to BACE1 transcription.

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References

  • Abd El Mohsen MM, Iravani MM, Spencer JP, Rose S, Fahim AT, Motawi TM, Ismail NA, Jenner P (2005) Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants. Biochem Biophys Res Commun 336:386–391

    PubMed  CAS  Google Scholar 

  • Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL, Finch CE, Frautschy S, Griffin WS, Hampel H, Hull M, Landreth G, Lue L, Mrak R, Mackenzie IR, McGeer PL, O’Banion MK, Pachter J, Pasinetti G, Plata-Salaman C, Rogers J, Rydel R, Shen Y, Streit W, Strohmeyer R, Tooyoma I, Van Muiswinkel FL, Veerhuis R, Walker D, Webster S, Wegrzyniak B, Wenk G, Wyss-Coray T (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421

    PubMed  CAS  Google Scholar 

  • Anantharaman M, Tangpong J, Keller JN, Murphy MP, Markesbery WR, Kiningham KK, St Clair DK (2006) Beta-amyloid mediated nitration of manganese superoxide dismutase: implication for oxidative stress in a APPNLH/NLH X PS-1P264L/P264L double knock-in mouse model of Alzheimer’s disease. Am J Pathol 168:1608–1618

    PubMed  CAS  Google Scholar 

  • Assefa Z, Valius M, Vántus T, Agostinis P, Merlevede W, Vandenheede JR (1999) JNK/SAPK activation by platelet-derived growth factor in A431 cells requires both the phospholipase C-gamma and the phosphatidylinositol 3-kinase signaling pathways of the receptor. Biochem Biophys Res Commun 261:641–645

    PubMed  CAS  Google Scholar 

  • Atwood CS, Perry G, Smith MA (2003) Cerebral hemorrhage and amyloid-beta. Science 299:1014

    PubMed  CAS  Google Scholar 

  • Bachman DL, Wolf PA, Linn RT, Knoefel JE, Cobb JL, Belanger AJ, White LR, D’Agostino RB (1993) Incidence of dementia and probable Alzheimer’s disease in a general population: the Framingham Study. Neurology 43:515–519

    PubMed  CAS  Google Scholar 

  • Barja G (2004) Free radicals and aging. Trends Neurosci 27:595–600

    PubMed  CAS  Google Scholar 

  • Barnham KJ, Haeffner F, Ciccotosto GD, Curtain CC, Tew D, Mavros C, Beyreuther K, Carrington D, Masters CL, Cherny RA, Cappai R, Bush AI (2004) Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer’s disease beta-amyloid. FASEB J 18:1427–1429

    PubMed  CAS  Google Scholar 

  • Behl C (2005) Oxidative stress in Alzheimer’s disease: implications for prevention and therapy. Subcell Biochem 38:65–78

    PubMed  CAS  Google Scholar 

  • Behl C, Moosmann B (2002) Antioxidant neuroprotection in Alzheimer’s disease as preventive and therapeutic approach. Free Radic Biol Med 33:182–191

    PubMed  CAS  Google Scholar 

  • Bell EL, Klimova TA, Eisenbart J, Moraes CT, Murphy MP, Budinger GR, Chandel NS (2007) The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J Cell Biol 177:1029–1036

    PubMed  CAS  Google Scholar 

  • Borghi R, Patriarca S, Traverso N, Piccini A, Storace D, Garuti A, Cirmena G, Odetti P, Tabaton M (2007) The increased activity of BACE1 correlates with oxidative stress in Alzheimer’s disease. Neurobiol Aging 28:1009–1014

    PubMed  CAS  Google Scholar 

  • Bourne KZ, Ferrari DC, Lange-Dohna C, Rossner S, Wood TG, Perez-Polo JR (2007) Differential regulation of BACE1 promoter activity by nuclear factor-kappaB in neurons and glia upon exposure to beta-amyloid peptides. J Neurosci Res 85:1194–1204

    PubMed  CAS  Google Scholar 

  • Brownlee M, Cerami A, Vlassara H (1988) Advanced products of nonenzymatic glycosylation and the pathogenesis of diabetic vascular disease. Diabetes Metab Rev 4:437–451

    PubMed  CAS  Google Scholar 

  • Bu G, Cam J, Zerbinatti C (2006) LRP in amyloid-beta production and metabolism. Ann N Y Acad Sci 1086:35–53

    PubMed  CAS  Google Scholar 

  • Bucala R, Cerami A (1992) Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol 23:1–34

    PubMed  CAS  Google Scholar 

  • Buggia-Prevot V, Sevalle J, Rossner S, Checler F (2008) NFkappaB-dependent control of BACE1 promoter transactivation by Abeta42. J Biol Chem 283:10037–10047

    PubMed  CAS  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 7:548–554

    PubMed  CAS  Google Scholar 

  • Carubelli R, Schneider JE Jr, Pye QN, Floyd RA (1995) Cytotoxic effects of autooxidative glycation. Free Radic Biol Med 18:265–269

    PubMed  CAS  Google Scholar 

  • Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci USA 95:11715–11720

    PubMed  CAS  Google Scholar 

  • Cheng SY, Trombetta LD (2004) The induction of amyloid precursor protein and alpha-synuclein in rat hippocampal astrocytes by diethyldithiocarbamate and copper with or without glutathione. Toxicol Lett 146:139–149

    PubMed  CAS  Google Scholar 

  • Cho HJ, Jin SM, Youn HD, Huh K, Mook-Jung I (2008) Disrupted intracellular calcium regulates BACE1 gene expression via nuclear factor of activated T cells 1 (NFAT 1) signaling. Aging Cell 7:137–147

    PubMed  CAS  Google Scholar 

  • Cho HJ, Son SM, Jin SM, Hong HS, Shin DH, Kim SJ, Huh K, Mook-Jung I (2009) RAGE regulates BACE1 and Abeta generation via NFAT1 activation in Alzheimer’s disease animal model. FASEB J 23:2639–2649

    PubMed  CAS  Google Scholar 

  • Christensen MA, Zhou W, Qing H, Lehman A, Philipsen S, Song W (2004) Transcriptional regulation of BACE1, the beta-amyloid precursor protein beta-secretase, by Sp1. Mol Cell Biol 24:865–874

    PubMed  CAS  Google Scholar 

  • Chui DH, Tanahashi H, Ozawa K, Ikeda S, Checler F, Ueda O, Suzuki H, Araki W, Inoue H, Shirotani K, Takahashi K, Gallyas F, Tabira T (1999) Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat Med 5:560–564

    PubMed  CAS  Google Scholar 

  • Citron M, Oltersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer’s disease increases beta-protein production. Nature 360:672–674

    PubMed  CAS  Google Scholar 

  • Citron M, Westaway D, Xia W, Carlson G, Diehl T, Levesque G, Johnson-Wood K, Lee M, Seubert P, Davis A, Kholodenko D, Motter R, Sherrington R, Perry B, Yao H, Strome R, Lieberburg I, Rommens J, Kim S, Schenk D, Fraser P, St George Hyslop P, Selkoe DJ (1997) Mutant presenilins of Alzheimer’s disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat Med 3:67–72

    PubMed  CAS  Google Scholar 

  • Colombo A, Repici M, Pesaresi M, Santambrogio S, Forloni G, Borsello T (2007) The TAT-JNK inhibitor peptide interferes with beta amyloid protein stability. Cell Death Differ 14:1845–1848

    PubMed  CAS  Google Scholar 

  • Colombo A, Bastone A, Ploia C, Sclip A, Salmona M, Forloni G, Borsello T (2009) JNK regulates APP cleavage and degradation in a model of Alzheimer’s disease. Neurobiol Dis 33:518–525

    PubMed  CAS  Google Scholar 

  • Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–923

    PubMed  CAS  Google Scholar 

  • Cordy JM, Hussain I, Dingwall C, Hooper NM, Turner AJ (2003) Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proc Natl Acad Sci USA 100:11735–11740

    PubMed  CAS  Google Scholar 

  • Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, Beal MF, Wallace DC (1992) Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age. Nat Genet 2:324–329

    PubMed  CAS  Google Scholar 

  • Costantini C, Della-Bianca V, Formaggio E, Chiamulera C, Montresor A, Rossi F (2005) The expression of p75 neurotrophin receptor protects against the neurotoxicity of soluble oligomers of beta-amyloid. Exp Cell Res 311:126–134

    PubMed  CAS  Google Scholar 

  • Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, Hatanpaa K, Troncoso JC, Mattson MP (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc Natl Acad Sci USA 101:2070–2075

    PubMed  CAS  Google Scholar 

  • Demuro A, Parker I, Stutzmann GE (2010) Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 285:12463–12468

    PubMed  CAS  Google Scholar 

  • Di X, Yan J, Zhao Y, Zhang J, Shi Z, Chang Y, Zhao B (2010) L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. Neuroscience 168:778–786

    PubMed  CAS  Google Scholar 

  • Dodart JC, Bales KR, Gannon KS, Greene SJ, DeMattos RB, Mathis C, DeLong CA, Wu S, Wu X, Holtzman DM, Paul SM (2002) Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer’s disease model. Nat Neurosci 5:452–457

    PubMed  CAS  Google Scholar 

  • Drouet B, Pinçon-Raymond M, Chambaz J, Pillot T (2000) Molecular basis of Alzheimer’s disease. Cell Mol Life Sci 57:705–715

    PubMed  CAS  Google Scholar 

  • Duff K, Eckman C, Zehr C, Yu X, Prada CM, Perez-tur J, Hutton M, Buee L, Harigaya Y, Yager D, Morgan D, Gordon MN, Holcomb L, Refolo L, Zenk B, Hardy J, Younkin S (1996) Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383:710–713

    PubMed  CAS  Google Scholar 

  • Evans RM, Hui S, Perkins A, Lahiri DK, Poirier J, Farlow MR (2004) Cholesterol and APOE genotype interact to influence Alzheimer disease progression. Neurology 62:1869–1871

    PubMed  CAS  Google Scholar 

  • Flood DG, Reaume AG, Dorfman KS, Lin YG, Lang DM, Trusko SP, Savage MJ, Annaert WG, De Strooper B, Siman R, Scott RW (2002) FAD mutant PS-1 gene-targeted mice: increased A beta 42 and A beta deposition without APP overproduction. Neurobiol Aging 23:335–348

    PubMed  CAS  Google Scholar 

  • Floyd RA, Hensley K (2002) Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging 23:795–807

    PubMed  CAS  Google Scholar 

  • Frederikse PH, Garland D, Zigler JS Jr, Piatigorsky J (1996) Oxidative stress increases production of beta-amyloid precursor protein and beta-amyloid (Abeta) in mammalian lenses, and Abeta has toxic effects on lens epithelial cells. J Biol Chem 271:10169–10174

    PubMed  CAS  Google Scholar 

  • Fukumori A, Okochi M, Tagami S, Jiang J, Itoh N, Nakayama T, Yanagida K, Ishizuka-Katsura Y, Morihara T, Kamino K, Tanaka T, Kudo T, Tanii H, Ikuta A, Haass C, Takeda M (2006) Presenilin-dependent gamma-secretase on plasma membrane and endosome is functionally distinct. Biochemistry 45:4907–4914

    PubMed  CAS  Google Scholar 

  • Fukumoto H, Cheung BS, Hyman BT, Irizarry MC (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 59:1381–1389

    PubMed  Google Scholar 

  • Gamba P, Leonarduzzi G, Tamagno E, Guglielmotto M, Testa G, Sottero B, Gargiulo S, Biasi F, Mauro A, Viña J, Poli G (2011) Interaction between 24-hydroxycholesterol, oxidative stress, and amyloid-β in amplifying neuronal damage in Alzheimer’s disease: three partners in crime. Aging Cell 10:403–417

    PubMed  CAS  Google Scholar 

  • Giliberto L, Borghi R, Piccini A, Mangerini R, Sorbi S, Cirmena G, Garuti A, Ghetti B, Tagliavini F, Mughal MR, Mattson MP, Zhu X, Wang X, Guglielmotto M, Tamagno E, Tabaton M (2009) Mutant presenilin 1 increases the expression and activity of BACE1. J Biol Chem 284:9027–9038

    PubMed  CAS  Google Scholar 

  • Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, Krafft GA, Klein WL (2003) Alzheimer’s disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci USA 100:10417–10422

    PubMed  CAS  Google Scholar 

  • Granic I, Dolga AM, Nijholt IM, van Dijk G, Eisel UL (2009) Inflammation and NF-kappaB in Alzheimer’s disease and diabetes. J Alzheimers Dis 16:809–821

    PubMed  Google Scholar 

  • Guglielmotto M, Aragno M, Autelli R, Giliberto L, Novo E, Colombatto S, Danni O, Parola M, Smith MA, Perry G, Tamagno E, Tabaton M (2009) The up-regulation of BACE1 mediated by hypoxia and ischemic injury: role of oxidative stress and HIF1alpha. J Neurochem 108:1045–1056

    PubMed  CAS  Google Scholar 

  • Guglielmotto M, Aragno M, Tamagno E, Vercellinatto I, Visentin S, Medana C, Catalano MG, Smith MA, Perry G, Danni O, Boccuzzi G, Tabaton M (2010) AGEs/RAGE complex upregulates BACE1 via NF-kappaB pathway activation. Neurobiol Aging [Epub ahead of print]

  • Guglielmotto M, Monteleone D, Giliberto L, Fornaro M, Borghi R, Tamagno E,Tabaton M (2011) Amyloid-β42 Activates the Expression of BACE1 Through the JNK Pathway. J Alzheimers Dis [Epub ahead of print]

  • Guidi I, Galimberti D, Lonati S, Novembrino C, Bamonti F, Tiriticco M, Fenoglio C, Venturelli E, Baron P, Bresolin N, Scarpini E (2006) Oxidative imbalance in patients with mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 27:262–269

    PubMed  CAS  Google Scholar 

  • Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12:383–388

    PubMed  CAS  Google Scholar 

  • Harman D (1992) Free radical theory of aging. Mutat Res 275:257–266

    PubMed  CAS  Google Scholar 

  • Hashimoto Y, Tsuji O, Niikura T, Yamagishi Y, Ishizaka M, Kawasumi M, Chiba T, Kanekura K, Yamada M, Tsukamoto E, Kouyama K, Terashita K, Aiso S, Lin A, Nishimoto I (2003) Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death. J Neurochem 84:864–877

    PubMed  CAS  Google Scholar 

  • Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, Floyd RA, Butterfield DA (1994) A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 91:3270–3274

    PubMed  CAS  Google Scholar 

  • Holsinger RM, McLean CA, Beyreuther K, Masters CL, Evin G (2002) Increased expression of the amyloid precursor beta-secretase in Alzheimer’s disease. Ann Neurol 51:783–786

    PubMed  CAS  Google Scholar 

  • Huang X, Cuajungco MP, Atwood CS, Hartshorn MA, Tyndall JD, Hanson GR, Stokes KC, Leopold M, Multhaup G, Goldstein LE, Scarpa RC, Saunders AJ, Lim J, Moir RD, Glabe C, Bowden EF, Masters CL, Fairlie DP, Tanzi RE, Bush AI (1999) Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 274:37111–37116

    PubMed  CAS  Google Scholar 

  • Ishii K, Tokuda T, Matsushima T, Miya F, Shoji S, Ikeda S, Tamaoka A (2003) Pravastatin at 10 mg/day does not decrease plasma levels of either amyloid-beta (Abeta) 40 or Abeta 42 in humans. Neurosci Lett 350:161–164

    PubMed  CAS  Google Scholar 

  • Jaeger S, Pietrzik CU (2008) Functional role of lipoprotein receptors in Alzheimer’s disease. Curr Alzheimer Res 5:15–25

    PubMed  CAS  Google Scholar 

  • Jellinger KA (2002) The pathology of ischemic-vascular dementia: an update. J Neurol Sci 203–204:153–157

    Google Scholar 

  • Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA (2000) Statins and the risk of dementia. Lancet 356:1627–1631

    PubMed  CAS  Google Scholar 

  • Jo DG, Arumugam TV, Woo HN, Park JS, Tang SC, Mughal M, Hyun DH, Park JH, Choi YH, Gwon AR, Camandola S, Cheng A, Cai H, Song W, Markesbery WR, Mattson MP (2010) Evidence that gamma-secretase mediates oxidative stress-induced beta-secretase expression in Alzheimer’s disease. Neurobiol Aging 31:917–925

    PubMed  CAS  Google Scholar 

  • Kandiah N, Feldman HH (2009) Therapeutic potential of statins in Alzheimer’s disease. J Neurol Sci 283:230–234

    PubMed  CAS  Google Scholar 

  • Kao SC, Krichevsky AM, Kosik KS, Tsai LH (2004) BACE1 suppression by RNA interference in primary cortical neurons. J Biol Chem 279:1942–1949

    PubMed  CAS  Google Scholar 

  • Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG (2003) Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300:486–489

    PubMed  CAS  Google Scholar 

  • Keller JN, Mattson MP (1998) Roles of lipid peroxidation in modulation of cellular signaling pathways, cell dysfunction, and death in the nervous system. Rev Neurosci 9:105–116

    PubMed  CAS  Google Scholar 

  • Keller JN, Schmitt FA, Scheff SW, Ding Q, Chen Q, Butterfield DA, Markesbery WR (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64:1152–1156

    PubMed  CAS  Google Scholar 

  • Kern A, Behl C (2009) The unsolved relationship of brain aging and late-onset Alzheimer disease. Biochim Biophys Acta 1790:1124–1132

    PubMed  CAS  Google Scholar 

  • Kirkitadze MD, Kowalska A (2005) Molecular mechanisms initiating amyloid beta-fibril formation in Alzheimer’s disease. Acta Biochim Pol 52:417–423

    PubMed  CAS  Google Scholar 

  • Klimova T, Chandel NS (2008) Mitochondrial complex III regulates hypoxic activation of HIF. Cell Death Differ 15:660–666

    PubMed  CAS  Google Scholar 

  • Koistinaho M, Ort M, Cimadevilla JM, Vondrous R, Cordell B, Koistinaho J, Bures J, Higgins LS (2001) Specific spatial learning deficits become severe with age in beta–amyloid precursor protein transgenic mice that harbor diffuse beta -amyloid deposits but do not form plaques. Proc Natl Acad Sci USA 98:14675–14680

    PubMed  CAS  Google Scholar 

  • Lagalwar S, Guillozet-Bongaarts AL, Berry RW, Binder LI (2006) Formation of phospho-SAPK/JNK granules in the hippocampus is an early event in Alzheimer disease. J Neuropathol Exp Neurol 65:455–464

    PubMed  Google Scholar 

  • Ledesma MD, Bonay P, Colaço C, Avila J (1994) Analysis of microtubule-associated protein tau glycation in paired helical filaments. J Biol Chem 269:21614–21619

    PubMed  CAS  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 2:1146–1150

    PubMed  CAS  Google Scholar 

  • Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, Ashe KH (2006) A specific amyloid-beta protein assembly in the brain impairs memory. Nature 440:352–357

    PubMed  Google Scholar 

  • Lovell MA, Markesbery WR (2001) Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol 58:392–396

    PubMed  CAS  Google Scholar 

  • Lütjohann D, Breuer O, Ahlborg G, Nennesmo I, Sidén A, Diczfalusy U, Björkhem I (1996) Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA 93:9799–9804

    PubMed  Google Scholar 

  • Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP (1997) A role for 4 hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. J Neurochem 68:255–264

    PubMed  CAS  Google Scholar 

  • Markesbery WR, Carney JM (1999) Oxidative alterations in Alzheimer’s disease. Brain Pathol 9:133–146

    PubMed  CAS  Google Scholar 

  • Markesbery WR, Lovell MA (1998) Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer’s disease. Neurobiol Aging 19:33–36

    PubMed  CAS  Google Scholar 

  • Markesbery WR, Kryscio RJ, Lovell MA, Morrow JD (2005) Lipid peroxidation is an early event in the brain in amnestic mild cognitive impairment. Ann Neurol 58:730–735

    PubMed  CAS  Google Scholar 

  • Mastrocola R, Guglielmotto M, Medana C, Catalano MG, Cutrupi S, Borghi R, Tamagno E, Boccuzzi G, Aragno M (2011) Dysregulation of SREBP2 induces BACE1 expression. Neurobiol Dis 44:116–124

    PubMed  CAS  Google Scholar 

  • Mielke MM, Lyketsos CG (2006) Lipids and the pathogenesis of Alzheimer’s disease: is there a link? Int Rev Psychiatry 18:173–186

    PubMed  Google Scholar 

  • Minopoli G, Stante M, Napolitano F, Telese F, Aloia L, De Felice M, Di Lauro R, Pacelli R, Brunetti A, Zambrano N, Russo T (2007) Essential roles for Fe65, Alzheimer amyloid precursor-binding protein, in the cellular response to DNA damage. J Biol Chem 282:831–835

    PubMed  CAS  Google Scholar 

  • Misonou H, Morishima-Kawashima M, Ihara Y (2000) Oxidative stress induces intracellular accumulation of amyloid beta-protein (Abeta) in human neuroblastoma cells. Biochemistry 39:6951–6959

    PubMed  CAS  Google Scholar 

  • Moosmann B, Behl C (2002) Antioxidants as treatment for neurodegenerative disorders. Expert Opin Investig Drugs 11:1407–1435

    PubMed  CAS  Google Scholar 

  • Murakami K, Irie K, Ohigashi H, Hara H, Nagao M, Shimizu T, Shirasawa T (2005) Formation stabilization model of the 42-mer Abeta radical: implications for the long-lasting oxidative stress in Alzheimer’s disease. J Am Chem Soc 127:15168–15174

    PubMed  CAS  Google Scholar 

  • Murray IV, Liu L, Komatsu H, Uryu K, Xiao G, Lawson JA, Axelsen PH (2007) Membrane-mediated amyloidogenesis and the promotion of oxidative lipid damage by amyloid beta proteins. J Biol Chem 282:9335–9345

    PubMed  CAS  Google Scholar 

  • Muscat S, Pelka J, Hegele J, Weigle B, Münch G, Pischetsrieder M (2007) Coffee and Maillard products activate NF-kappaB in macrophages via H2O2 production. Mol Nutr Food Res 51:525–535

    PubMed  CAS  Google Scholar 

  • Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267:14998–15004

    PubMed  CAS  Google Scholar 

  • Nunomura A, Perry G, Hirai K, Aliev G, Takeda A, Chiba S, Smith MA (1999) Neuronal RNA oxidation in Alzheimer’s disease and Down’s syndrome. Ann N Y Acad Sci 893:362–364

    PubMed  CAS  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 60:759–767

    PubMed  CAS  Google Scholar 

  • Ortega-Pérez I, Cano E, Were F, Villar M, Vázquez J, Redondo JM (2005) c-Jun N-terminal kinase (JNK) positively regulates NFATc2 transactivation through phosphorylation within the N-terminal regulatory domain. J Biol Chem 280:20867–20878

    PubMed  Google Scholar 

  • Panza F, Capurso C, D’Introno A, Colacicco AM, De Candia D, Capurso A, Solfrizzi V (2007) Total cholesterol levels and the risk of mild cognitive impairment and Alzheimer’s disease. J Am Geriatr Soc 55:133–135

    PubMed  Google Scholar 

  • Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D, Zaccheo D, Odetti P, Strocchi P, Marinari UM, Tabaton M, Pronzato MA (2000) Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun 268:642–646

    PubMed  CAS  Google Scholar 

  • Pappolla MA, Omar RA, Kim KS, Robakis NK (1992) Immunohistochemical evidence of oxidative stress in Alzheimer‘s disease. Am J Pathol 14:621–628

    Google Scholar 

  • Passer B, Pellegrini L, Russo C, Siegel RM, Lenardo MJ, Schettini G, Bachmann M, Tabaton M, D’Adamio L (2000) Generation of an apoptotic intracellular peptide by gamma-secretase cleavage of Alzheimer’s amyloid beta protein precursor. J Alzheimers Dis 2:289–301

    PubMed  CAS  Google Scholar 

  • Patil S, Sheng L, Masserang A, Chan C (2006) Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons. Neurosci Lett 406:55–59

    PubMed  CAS  Google Scholar 

  • Perry G, Nunomura A, Hirai K, Takeda A, Aliev G, Smith MA (2000) Oxidative damage in Alzheimer’s disease: the metabolic dimension. Int J Dev Neurosci 18:417–421

    PubMed  CAS  Google Scholar 

  • Praticò D (2008) Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 29:609–615

    PubMed  Google Scholar 

  • Puglielli L, Tanzi RE, Kovacs DM (2003) Alzheimer’s disease: the cholesterol connection. Nat Neurosci 6:345–351

    PubMed  CAS  Google Scholar 

  • Puig B, Gómez-Isla T, Ribé E, Cuadrado M, Torrejón-Escribano B, Dalfó E, Ferrer I (2004) Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA plaques in APP Tg2576 mice. Neuropathol Appl Neurobiol 30:491–502

    PubMed  CAS  Google Scholar 

  • Qin J, Goswami R, Dawson S, Dawson G (2008) Expression of the receptor for advanced glycation end products in oligodendrocytes in response to oxidative stress. J Neurosci Res 86:2414–2422

    PubMed  CAS  Google Scholar 

  • Resende R, Ferreiro E, Pereira C, Resende de Oliveira C (2008) Neurotoxic effect of oligomeric and fibrillar species of amyloid-beta peptide 1–42: involvement of endoplasmic reticulum calcium release in oligomer-induced cell death. Neuroscience 155:725–737

    PubMed  CAS  Google Scholar 

  • Rocchi A, Orsucci D, Tognoni G, Ceravolo R, Siciliano G (2009) The role of vascular factors in late-onset sporadic Alzheimer’s disease. Genetic and molecular aspects. Curr Alzheimer Res 6:224–237

    PubMed  CAS  Google Scholar 

  • Rodrigues Siqueira I, Fochesatto C, da Silva Torres IL, Dalmaz C, Alexandre Netto C (2005) Aging affects oxidative state in hippocampus, hypothalamus and adrenal glands of Wistar rats. Life Sci 78:271–278

    PubMed  CAS  Google Scholar 

  • Rogers JT, Randall JD, Cahill CM, Eder PS, Huang X, Gunshin H, Leiter L, McPhee J, Sarang SS, Utsuki T, Greig NH, Lahiri DK, Tanzi RE, Bush AI, Giordano T, Gullans SR (2002) An iron-responsive element type II in the 5′-untranslated region of the Alzheimer’s amyloid precursor protein transcript. J Biol Chem 277:24558–45518

    Google Scholar 

  • Sambamurti K, Kinsey R, Maloney B, Ge YW, Lahiri DK (2004) Gene structure and organization of the human beta-secretase (BACE) promoter. FASEB J 18:1034–1036

    PubMed  CAS  Google Scholar 

  • Sastre M, Dewachter I, Rossner S, Bogdanovic N, Rosen E, Borghgraef P, Evert BO, Dumitrescu-Ozimek L, Thal DR, Landreth G, Walter J, Klockgether T, van Leuven F, Heneka MT (2006) Nonsteroidal anti-inflammatory drugs repress beta-secretase gene promoter activity by the activation of PPARgamma. Proc Natl Acad Sci USA 103:443–448

    PubMed  CAS  Google Scholar 

  • Sayre LM, Zagorski MG, Surewicz WK, Krafft GA, Perry G (1997) Mechanisms of neurotoxicity associated with amyloid beta deposition and the role of free radicals in the pathogenesis of Alzheimer’s disease: a critical appraisal. Chem Res Toxicol 10:518–526

    PubMed  CAS  Google Scholar 

  • Schneider JA, Wilson RS, Cochran EJ, Bienias JL, Arnold SE, Evans DA, Bennett DA (2003) Relation of cerebral infarctions to dementia and cognitive function in older persons. Neurology 60:1082–1088

    PubMed  CAS  Google Scholar 

  • Serrano-Pozo A, Vega GL, Lütjohann D, Locascio JJ, Tennis MK, Deng A, Atri A, Hyman BT, Irizarry MC, Growdon JH (2010) Effects of simvastatin on cholesterol metabolism and Alzheimer disease biomarkers. Alzheimer Dis Assoc Disord 24:220–226

    PubMed  CAS  Google Scholar 

  • Singh M, Nam DT, Arseneault M, Ramassamy C (2010) Role of by-products of lipid oxidation in Alzheimer’s disease brain: a focus on acrolein. J Alzheimers Dis 21:741–756

    PubMed  CAS  Google Scholar 

  • Smith MA, Taneda S, Richey PL, Miyata S, Yan SD, Stern D, Sayre LM, Monnier VM, Perry G (1994) Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci USA 91:5710–5714

    PubMed  CAS  Google Scholar 

  • Smith MA, Rudnicka-Nawrot M, Richey PL, Praprotnik D, Mulvihill P, Miller CA, Sayre LM, Perry G (1995) Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer’s disease. J Neurochem 64:2660–2666

    PubMed  CAS  Google Scholar 

  • Song F, Poljak A, Smythe GA, Sachdev P (2009) Plasma biomarkers for mild cognitive impairment and Alzheimer’s disease. Brain Res Rev 61:69–80

    PubMed  CAS  Google Scholar 

  • Sultana R, Perluigi M, Butterfield DA (2009) Oxidatively modified proteins in Alzheimer’s disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis. Acta Neuropathol 118:131–150

    PubMed  CAS  Google Scholar 

  • Sun X, He G, Qing H, Zhou W, Dobie F, Cai F, Staufenbiel M, Huang LE, Song W (2006) Hypoxia facilitates Alzheimer’s disease pathogenesis by up-regulating BACE1 gene expression. Proc Natl Acad Sci USA 103:18727–18732

    PubMed  CAS  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 280:35789–35792

    PubMed  CAS  Google Scholar 

  • Tagami S, Okochi M, Fukumori A, Jiang J, Yanagida K, Nakayama T, Morihara T, Tanaka T, Kudo T, Takeda M (2008) Processes of beta-amyloid and intracellular cytoplasmic domain generation by presenilin/gamma-secretase. Neurodegener Dis 5:160–162

    PubMed  CAS  Google Scholar 

  • Takeuchi M, Makita Z (2001) Alternative routes for the formation of immunochemically distinct advanced glycation end-products in vivo. Curr Mol Med 1:305–315

    PubMed  CAS  Google Scholar 

  • Tamagno E, Bardini P, Obbili A, Vitali A, Borghi R, Zaccheo D, Pronzato MA, Danni O, Smith MA, Perry G, Tabaton M (2002) Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol Dis 10:279–288

    PubMed  CAS  Google Scholar 

  • Tamagno E, Guglielmotto M, Bardini P, Santoro G, Davit A, Di Simone D, Danni O, Tabaton M (2003) Dehydroepiandrosterone reduces expression and activity of BACE in NT2 neurons exposed to oxidative stress. Neurobiol Dis 14:291–301

    PubMed  CAS  Google Scholar 

  • Tamagno E, Parola M, Bardini P, Piccini A, Borghi R, Guglielmotto M, Santoro G, Davit A, Danni O, Smith MA, Perry G, Tabaton M (2005) Beta-site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways. J Neurochem 92:628–636

    PubMed  CAS  Google Scholar 

  • Tamagno E, Bardini P, Guglielmotto M, Danni O, Tabaton M (2006) The various aggregation states of beta-amyloid 1–42 mediate different effects on oxidative stress, neurodegeneration, and BACE-1 expression. Free Radic Biol Med 41:202–212

    PubMed  CAS  Google Scholar 

  • Tamagno E, Guglielmotto M, Aragno M, Borghi R, Autelli R, Giliberto L, Muraca G, Danni O, Zhu X, Smith MA, Perry G, Jo DG, Mattson MP, Tabaton M (2008) Oxidative stress activates a positive feedback between the gamma- and beta-secretase cleavages of the beta-amyloid precursor protein. J Neurochem 104:683–695

    PubMed  CAS  Google Scholar 

  • Tong Y, Zhou W, Fung V, Christensen MA, Qing H, Sun X, Song W (2005) Oxidative stress potentiates BACE1 gene expression and Abeta generation. J Neural Transm 112:455–469

    PubMed  CAS  Google Scholar 

  • Turrens JF (2003) Mitochondrial formation of reactive oxygen species. J Physiol 552:335–344

    PubMed  CAS  Google Scholar 

  • Vermeer SE, Prins ND, den Heijer T, Hofman A, Koudstaal PJ, Breteler MM (2003) Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 348:1215–1222

    PubMed  Google Scholar 

  • Vieira M, Fernandes J, Burgeiro A, Thomas GM, Huganir RL, Duarte CB, Carvalho AL, Santos AE (2010) Excitotoxicity through Ca2+-permeable AMPA receptors requires Ca2+-dependent JNK activation. Neurobiol Dis 40:645–655

    PubMed  CAS  Google Scholar 

  • Vitek MP, Bhattacharya K, Glendening JM, Stopa E, Vlassara H, Bucala R, Manogue K, Cerami A (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA 91:4766–47670

    PubMed  CAS  Google Scholar 

  • Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA (2005) Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. J Neurochem 93:953–962

    PubMed  CAS  Google Scholar 

  • Wen Y, Yu WH, Maloney B, Bailey J, Ma J, Marié I, Maurin T, Wang L, Figueroa H, Herman M, Krishnamurthy P, Liu L, Planel E, Lau LF, Lahiri DK, Duff K (2008) Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron 57:680–690

    PubMed  CAS  Google Scholar 

  • Wolozin B (2004) Cholesterol and the biology of Alzheimer’s disease. Neuron 41:7–10

    PubMed  CAS  Google Scholar 

  • Wu CY, Hsieh HL, Sun CC, Yang CM (2009) IL-1beta induces MMP-9 expression via a Ca2+-dependent CaMKII/JNK/c-JUN cascade in rat brain astrocytes. Glia 57:1775–1789

    PubMed  Google Scholar 

  • Yaar M, Zhai S, Panova I, Fine RE, Eisenhauer PB, Blusztajn JK, Lopez-Coviella I, Gilchrest BA (2007) A cyclic peptide that binds p75(NTR) protects neurones from beta amyloid(1–40)-induced cell death. Neuropathol Appl Neurobiol 33:533–543

    PubMed  CAS  Google Scholar 

  • Yan SD, Chen X, Schmidt AM, Brett J, Godman G, Zou YS, Scott CW, Caputo C, Frappier T, Smith MA (1994) Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci USA 91:7787–7791

    PubMed  CAS  Google Scholar 

  • Yan SD, Yan SF, Chen X, Fu J, Chen M, Kuppusamy P, Smith MA, Perry G, Godman GC, Nawroth P (1995) Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide. Nat Med 1:693–699

    PubMed  CAS  Google Scholar 

  • Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, Slattery T, Zhao L, Nagashima M, Morser J, Migheli A, Nawroth P, Stern D, Schmidt AM (1996) RAGE and amyloid-beta peptide neurotoxicity in Alzheimer’s disease. Nature 382:685–691

    PubMed  CAS  Google Scholar 

  • Yang LB, Lindholm K, Yan R, Citron M, Xia W, Yang XL, Beach T, Sue L, Wong P, Price D, Li R, Shen Y (2003) Elevated beta-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nat Med 9:3–4

    PubMed  CAS  Google Scholar 

  • Yankner BA (1996) Mechanisms of neuronal degeneration in Alzheimer’s disease. Neuron 16:921–932

    PubMed  CAS  Google Scholar 

  • Yatin SM, Varadarajan S, Link CD, Butterfield DA (1999) In vitro and in vivo oxidative stress associated with Alzheimer’s amyloid beta-peptide (1-42). Neurobiol Aging 20:325–330

    PubMed  CAS  Google Scholar 

  • Yoshida H, Hastie CJ, McLauchlan H, Cohen P, Goedert M (2004) Phosphorylation of microtubule-associated protein tau by isoforms of c-Jun N-terminal kinase (JNK). J Neurochem 90:352–358

    PubMed  CAS  Google Scholar 

  • Zhang X, Zhou K, Wang R, Cui J, Lipton SA, Liao FF, Xu H, Zhang YW (2007) Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. J Biol Chem 282:10873–10880

    PubMed  CAS  Google Scholar 

  • Zhao J, Fu Y, Yasvoina M, Shao P, Hitt B, O’Connor T, Logan S, Maus E, Citron M, Berry R, Binder L, Vassar R (2007) Beta-site amyloid precursor protein cleaving enzyme 1 levels become elevated in neurons around amyloid plaques: implications for Alzheimer’s disease pathogenesis. J Neurosci 27:3639–3649

    PubMed  CAS  Google Scholar 

  • Zhu X, Ogawa O, Wang Y, Perry G, Smith MA (2003a) JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer’s disease. J Neurochem 85:87–93

    PubMed  CAS  Google Scholar 

  • Zhu X, Raina AK, Lee HG, Chao M, Nunomura A, Tabaton M, Petersen RB, Perry G, Smith MA (2003b) Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways. Antioxid Redox Signal 5:571–576

    PubMed  CAS  Google Scholar 

  • Zhu Y, Carvey PM, Ling Z (2006) Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res 1090:35–44

    PubMed  CAS  Google Scholar 

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Acknowledgments

The study was supported by Italian Ministry of Health, Regione Piemonte (ET) and CARIGE (MT).

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Authors and Affiliations

  1. General Pathology Section, Department of Experimental Medicine and Oncology, University of Torino, Corso Raffaello 30, 10125, Turin, Italy

    Elena Tamagno, Michela Guglielmotto & Debora Monteleone

  2. Neuroscience Institute of the Cavalieri Ottolenghi Foundation (NICO), University of Torino, Corso Raffaello 30, 10125, Turin, Italy

    Elena Tamagno, Michela Guglielmotto & Debora Monteleone

  3. Unit of Geriatric Medicine, Department of Internal Medicine, University of Genova, 16132, Genoa, Italy

    Massimo Tabaton

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  1. Elena Tamagno
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  2. Michela Guglielmotto
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  4. Massimo Tabaton
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Correspondence to Elena Tamagno or Massimo Tabaton.

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Tamagno, E., Guglielmotto, M., Monteleone, D. et al. Amyloid-β Production: Major Link Between Oxidative Stress and BACE1. Neurotox Res 22, 208–219 (2012). https://doi.org/10.1007/s12640-011-9283-6

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