The role of NADPH oxidase (NOX) enzymes in neurodegenerative disease

Abstract

Recently, mounting evidence implicating reactive oxygen species (ROS) generated by NADPH oxidase (NOX) enzymes in the pathogenesis of several neurodegenerative diseases including Amyotrophic lateral sclerosis (ALS), Alzheimer’s (AD), Parkinson’s (PD) and polyglutamine disease, have arisen. NOX enzymes are transmembrane proteins and generate reactive oxygen species by transporting electrons across lipid membranes. Under normal healthy conditions, low levels of ROS produced by NOX enzymes have been shown to play a role in neuronal differentiation and synaptic plasticity. However, in chronic neurodegenerative diseases over-activation of NOX in neurons, as well as in astrocytes and microglia, has been linked to pathogenic processes such as oxidative stress, exitotoxicity and neuroinflammation. In this review, we summarize the current knowledge about NOX functions in the healthy central nervous system and especially the role of NOX enzymes in neurodegenerative disease processes.

Keywords

neurodegeneration / oxidative stress / NADPH oxidase / microglia / inflammation

References

[1] Abeti R, Abramov A Y, Duchen M R (2011). Beta-amyloid activates PARP causing astrocytic metabolic failure and neuronal death. Brain, 134(Pt 6): 1658-1672

[2] Abramov A Y, Canevari L, Duchen M R (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

[3] Abramov A Y, Jacobson J, Wientjes F, Hothersall J, Canevari L, Duchen M R (2005). Expression and modulation of an NADPH oxidase in mammalian astrocytes. J Neurosci, 25(40): 9176-9184

[4] Ajayi A, Yu X, Lindberg S, Langel U, Ström A L (2012). Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model. BMC Neurosci, 13(1): 86

[5] Amaral J D, Xavier J M, Steer C J, Rodrigues C M (2010). The role of p53 in apoptosis. Discov Med, 9(45): 145-152

[6] Anantharam V, Kaul S, Song C, Kanthasamy A, Kanthasamy A G (2007). Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells. Neurotoxicology, 28(5): 988-997

[7] Ansari M A, Scheff S W (2011). NADPH-oxidase activation and cognition in Alzheimer disease progression. Free Radic Biol Med, 51(1): 171-178

[8] Atkins C M, Sweatt J D (1999). Reactive oxygen species mediate activity-dependent neuron-glia signaling in output fibers of the hippocampus. J Neurosci, 19(17): 7241-7248

[9] Bánfi B, Malgrange B, Knisz J, Steger K, Dubois-Dauphin M, Krause K H (2004). NOX3, a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem, 279(44): 46065-46072

[10] Barber S C, Shaw P J (2010). Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radic Biol Med, 48(5): 629-641

[11] Barger S W, Goodwin M E, Porter M M, Beggs M L (2007). Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation. J Neurochem, 101(5): 1205-1213

[12] Barnham K J, Masters C L, Bush A I (2004). Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov, 3(3): 205-214

[13] Bäumer A T, Ten Freyhaus H, Sauer H, Wartenberg M, Kappert K, Schnabel P, Konkol C, Hescheler J, Vantler M, Rosenkranz S (2008). Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species. J Biol Chem, 283(12): 7864-7876

[14] Bedard K, Krause K H (2007). The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev, 87(1): 245-313

[15] Benarroch E E (2005). Neuron-astrocyte interactions: partnership for normal function and disease in the central nervous system. Mayo Clin Proc, 80(10): 1326-1338

[16] Bertoni A, Giuliano P, Galgani M, Rotoli D, Ulianich L, Adornetto A, Santillo M R, Porcellini A, Avvedimento V E (2011). Early and late events induced by polyQ-expanded proteins: identification of a common pathogenic property of polYQ-expanded proteins. J Biol Chem, 286(6): 4727-4741

[17] Bhatt L, Groeger G, McDermott K, Cotter T G (2010). Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system. Mol Vis, 16: 283-293

[18] Bianca V D, Dusi S, Bianchini E, Dal Prà I, Rossi F (1999). beta-amyloid activates the O-2 forming NADPH oxidase in microglia, monocytes, and neutrophils. A possible inflammatory mechanism of neuronal damage in Alzheimer’s disease. J Biol Chem, 274(22): 15493-15499

[19] Block M L, Zecca L, Hong J S (2007). Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci, 8(1): 57-69

[20] Boillée S, Yamanaka K, Lobsiger C S, Copeland N G, Jenkins N A, Kassiotis G, Kollias G, Cleveland D W (2006). Onset and progression in inherited ALS determined by motor neurons and microglia. Science, 312(5778): 1389-1392

[21] Bokoch G M, Diebold B, Kim J S, Gianni D (2009). Emerging evidence for the importance of phosphorylation in the regulation of NADPH oxidases. Antioxid Redox Signal, 11(10): 2429-2441

[22] Brennan A M, Suh S W, Won S J, Narasimhan P, Kauppinen T M, Lee H, Edling Y, Chan P H, Swanson R A (2009). NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci, 12(7): 857-863

[23] Brown D I, Griendling K K (2009). Nox proteins in signal transduction. Free Radic Biol Med, 47(9): 1239-1253

[24] Bruce-Keller A J, Gupta S, Knight A G, Beckett T L, McMullen J M, Davis P R, Murphy M P, Van Eldik L J, St Clair D, Keller J N (2011). Cognitive impairment in humanized APP×PS1 mice is linked to Aβ(1-2) and NOX activation. Neurobiol Dis, 44(3): 317-326

[25] Bruce-Keller A J, Gupta S, Parrino T E, Knight A G, Ebenezer P J, Weidner A M, LeVine H 3rd, Keller J N, Markesbery W R (2010). NOX activity is increased in mild cognitive impairment. Antioxid Redox Signal, 12(12): 1371-1382

[26] Caunt C J, Keyse S M (2012) Dual-specificity MAP kinase phosphatases (MKPs). FEBS J.

[27] Cavaliere F, Urra O, Alberdi E, Matute C (2012). Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate. Cell Death Dis, 3(2): e268

[28] Chaitanya G V, Steven A J, Babu P P (2010). PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal, 8(1): 31

[29] Chen K, Craige S E, Keaney J F Jr (2009). Downstream targets and intracellular compartmentalization in Nox signaling. Antioxid Redox Signal, 11(10): 2467-2480

[30] Cheng G, Ritsick D, Lambeth J D (2004). Nox3 regulation by NOXO1, p47phox, and p67phox. J Biol Chem, 279(33): 34250-34255

[31] Chéret C, Gervais A, Lelli A, Colin C, Amar L, Ravassard P, Mallet J, Cumano A, Krause K H, Mallat M (2008). Neurotoxic activation of microglia is promoted by a nox1-dependent NADPH oxidase. J Neurosci, 28(46): 12039-12051

[32] Choi S H, Aid S, Kim H W, Jackson S H, Bosetti F (2012). Inhibition of NADPH oxidase promotes alternative and anti-inflammatory microglial activation during neuroinflammation. J Neurochem, 120(2): 292-301

[33] Coraci I S, Husemann J, Berman J W, Hulette C, Dufour J H, Campanella G K, Luster A D, Silverstein S C, El-Khoury J B (2002). CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer’s disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am J Pathol, 160(1): 101-112

[34] Costa R O, Lacor P N, Ferreira I L, Resende R, Auberson Y P, Klein W L, Oliveira C R, Rego A C, Pereira C M (2012). Endoplasmic reticulum stress occurs downstream of GluN2B subunit of N-methyl-d-aspartate receptor in mature hippocampal cultures treated with amyloid-β oligomers. Aging Cell, 11(5): 823-833

[35] Coyoy A, Valencia A, Guemez-Gamboa A, Morán J (2008). Role of NADPH oxidase in the apoptotic death of cultured cerebellar granule neurons. Free Radic Biol Med, 45(8): 1056-1064

[36] Cristóvão A C, Choi D H, Baltazar G, Beal M F, Kim Y S (2009). The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell death. Antioxid Redox Signal, 11(9): 2105-2118

[37] Cross A R (2000). p40(phox) Participates in the activation of NADPH oxidase by increasing the affinity of p47(phox) for flavocytochrome b(558). Biochem J, 349(Pt 1): 113-117

[38] Damiano S, Fusco R, Morano A, De Mizio M, Paternò R, De Rosa A, Spinelli R, Amente S, Frunzio R, Mondola P, Miot F, Laccetti P, Santillo M, Avvedimento E V (2012). Reactive oxygen species regulate the levels of dual oxidase (Duox1-2) in human neuroblastoma cells. PLoS ONE, 7(4): e34405

[39] DeLeo F R, Allen L A, Apicella M, Nauseef W M (1999). NADPH oxidase activation and assembly during phagocytosis. J Immunol, 163(12): 6732-6740

[40] DeLeo F R, Burritt J B, Yu L, Jesaitis A J, Dinauer M C, Nauseef W M (2000). Processing and maturation of flavocytochrome b558 include incorporation of heme as a prerequisite for heterodimer assembly. J Biol Chem, 275(18): 13986-13993

[41] Di Maio R, Mastroberardino P G, Hu X, Montero L, Greenamyre J T (2011). Pilocapine alters NMDA receptor expression and function in hippocampal neurons: NADPH oxidase and ERK1/2 mechanisms. Neurobiol Dis, 42(3): 482-495

[42] Dickinson B C, Peltier J, Stone D, Schaffer D V, Chang C J (2011). Nox2 redox signaling maintains essential cell populations in the brain. Nat Chem Biol, 7(2): 106-112

[43] Diebold B A, Bokoch G M (2001). Molecular basis for Rac2 regulation of phagocyte NADPH oxidase. Nat Immunol, 2(3): 211-215

[44] Dumont M, Stack C, Elipenhali C, Calingasan N Y, Wille E, Beal M F (2011). Apocynin administration does not improve behavioral and neuropathological deficits in a transgenic mouse model of Alzheimer’s disease. Neurosci Lett, 492(3): 150-154

[45] Dunckley T, Huentelman M J, Craig D W, Pearson J V, Szelinger S, Joshipura K, Halperin R F, Stamper C, Jensen K R, Letizia D, Hesterlee S E, Pestronk A, Levine T, Bertorini T, Graves M C, Mozaffar T, Jackson C E, Bosch P, McVey A, Dick A, Barohn R, Lomen-Hoerth C, Rosenfeld J, O’connor D T, Zhang K, Crook R, Ryberg H, Hutton M, Katz J, Simpson E P, Mitsumoto H, Bowser R, Miller R G, Appel S H, Stephan D A (2007). Whole-genome analysis of sporadic amyotrophic lateral sclerosis. N Engl J Med, 357(8): 775-788

[46] Dvorakova M, Höhler B, Richter E, Burritt J B, Kummer W (1999). Rat sensory neurons contain cytochrome b558 large subunit immunoreactivity. Neuroreport, 10(12): 2615-2617

[47] Fatokun A A, Stone T W, Smith R A (2008). Oxidative stress in neurodegeneration and available means of protection. Front Biosci, 13(13): 3288-3311

[48] Federico A, Cardaioli E, Da Pozzo P, Formichi P, Gallus GN, Radi E (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci.

[49] Gao H M, Zhou H, Hong J S (2012). NADPH oxidases: novel therapeutic targets for neurodegenerative diseases. Trends Pharmacol Sci, 33(6): 295-303

[50] Girouard H, Wang G, Gallo E F, Anrather J, Zhou P, Pickel V M, Iadecola C (2009). NMDA receptor activation increases free radical production through nitric oxide and NOX2. J Neurosci, 29(8): 2545-2552

[51] Gough D R, Cotter T G (2011). Hydrogen peroxide: a Jekyll and Hyde signalling molecule. Cell Death Dis, 2(10): e213

[52] Grasberger H, Refetoff S (2006). Identification of the maturation factor for dual oxidase. Evolution of an eukaryotic operon equivalent. J Biol Chem, 281(27): 18269-18272

[53] Grimm S, Hoehn A, Davies K J, Grune T (2011). Protein oxidative modifications in the ageing brain: consequence for the onset of neurodegenerative disease. Free Radic Res, 45(1): 73-88

[54] Groeger G, Mackey A M, Pettigrew C A, Bhatt L, Cotter T G (2009). Stress-induced activation of Nox contributes to cell survival signalling via production of hydrogen peroxide. J Neurochem, 109(5): 1544-1554

[55] Groemping Y, Rittinger K (2005). Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J, 386(Pt 3): 401-416

[56] Halliwell B (2001). Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging, 18(9): 685-716

[57] Han C H, Freeman J L, Lee T, Motalebi S A, Lambeth J D (1998). Regulation of the neutrophil respiratory burst oxidase. Identification of an activation domain in p67(phox). J Biol Chem, 273(27): 16663-16668

[58] Harraz M M, Marden J J, Zhou W, Zhang Y, Williams A, Sharov V S, Nelson K, Luo M, Paulson H, Schöneich C, Engelhardt J F (2008). SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest, 118(2): 659-670

[59] Harrigan T J, Abdullaev I F, Jourd’heuil D, Mongin A A (2008). Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: the role of NADPH oxidases. J Neurochem, 106(6): 2449-2462

[60] He Y, Cui J, Lee J C, Ding S, Chalimoniuk M, Simonyi A, Sun A Y, Gu Z, Weisman G A, Wood W G, Sun G Y (2011). Prolonged exposure of cortical neurons to oligomeric amyloid-β impairs NMDA receptor function via NADPH oxidase-mediated ROS production: protective effect of green tea (-)-epigallocatechin-3-gallate. ASN Neuro, 3(1): e00050

[61] Heumüller S, Wind S, Barbosa-Sicard E, Schmidt H H, Busse R, Schröder K, Brandes R P (2008). Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension, 51(2): 211-217

[62] Hsieh H L, Lin C C, Shih R H, Hsiao L D, Yang C M (2012). NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes. J Neuroinflammation, 9(1): 110

[63] Huang J, Hitt N D, Kleinberg M E (1995). Stoichiometry of p22-phox and gp91-phox in phagocyte cytochrome b558. Biochemistry, 34(51): 16753-16757

[64] Huo Y, Rangarajan P, Ling E A, Dheen S T (2011). Dexamethasone inhibits the Nox-dependent ROS production via suppression of MKP-1-dependent MAPK pathways in activated microglia. BMC Neurosci, 12(1): 49

[65] Ibi M, Katsuyama M, Fan C, Iwata K, Nishinaka T, Yokoyama T, Yabe-Nishimura C (2006). NOX1/NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth. Free Radic Biol Med, 40(10): 1785-1795

[66] Jana A, Pahan K (2004). Fibrillar amyloid-beta peptides kill human primary neurons via NADPH oxidase-mediated activation of neutral sphingomyelinase. Implications for Alzheimer’s disease. J Biol Chem, 279(49): 51451-51459

[67] Jiang F, Zhang Y, Dusting G J (2011). NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev, 63(1): 218-242

[68] Kahles T, Brandes R P (2012) Which NADPH oxidase isoform is relevant for ischemic stroke? The case for Nox 2. Antioxid Redox Signal.

[69] Katsuyama M, Matsuno K, Yabe-Nishimura C (2012). Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme. J Clin Biochem Nutr, 50(1): 9-22

[70] Kauppinen T M, Swanson R A (2007). The role of poly(ADP-ribose) polymerase-1 in CNS disease. Neuroscience, 145(4): 1267-1272

[71] Kawahara T, Ritsick D, Cheng G, Lambeth J D (2005). Point mutations in the proline-rich region of p22phox are dominant inhibitors of Nox1- and Nox2-dependent reactive oxygen generation. J Biol Chem, 280(36): 31859-31869

[72] Kettenmann H, Hanisch U K, Noda M, Verkhratsky A (2011). Physiology of microglia. Physiol Rev, 91(2): 461-553

[73] Kishida K T, Hoeffer C A, Hu D, Pao M, Holland S M, Klann E (2006). Synaptic plasticity deficits and mild memory impairments in mouse models of chronic granulomatous disease. Mol Cell Biol, 26(15): 5908-5920

[74] Kishida K T, Pao M, Holland S M, Klann E (2005). NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. J Neurochem, 94(2): 299-306

[75] Kiss P J, Knisz J, Zhang Y, Baltrusaitis J, Sigmund C D, Thalmann R, Smith R J, Verpy E, Bánfi B (2006). Inactivation of NADPH oxidase organizer 1 results in severe imbalance. Curr Biol, 16(2): 208-213

[76] Knapp L T, Klann E (2002). Role of reactive oxygen species in hippocampal long-term potentiation: contributory or inhibitory? J Neurosci Res, 70(1): 1-7

[77] Koga H, Terasawa H, Nunoi H, Takeshige K, Inagaki F, Sumimoto H (1999). Tetratricopeptide repeat (TPR) motifs of p67(phox) participate in interaction with the small GTPase Rac and activation of the phagocyte NADPH oxidase. J Biol Chem, 274(35): 25051-25060

[78] Lapouge K, Smith S J, Groemping Y, Rittinger K (2002). Architecture of the p40-p47-p67phox complex in the resting state of the NADPH oxidase. A central role for p67phox. J Biol Chem, 277(12): 10121-10128

[79] Lapouge K, Smith S J, Walker P A, Gamblin S J, Smerdon S J, Rittinger K (2000). Structure of the TPR domain of p67phox in complex with Rac.GTP. Mol Cell, 6(4): 899-907

[80] Lavigne M C, Malech H L, Holland S M, Leto T L (2001). Genetic requirement of p47phox for superoxide production by murine microglia. FASEB J, 15(2): 285-287

[81] Li B, Bedard K, Sorce S, Hinz B, Dubois-Dauphin M, Krause K H (2009). NOX4 expression in human microglia leads to constitutive generation of reactive oxygen species and to constitutive IL-6 expression. J Innate Immun, 1(6): 570-581

[82] Li Q, Spencer N Y, Pantazis N J, Engelhardt J F (2011). Alsin and SOD1(G93A) proteins regulate endosomal reactive oxygen species production by glial cells and proinflammatory pathways responsible for neurotoxicity. J Biol Chem, 286(46): 40151-40162

[83] Liu Q, Kang J H, Zheng R L (2005). NADPH oxidase produces reactive oxygen species and maintains survival of rat astrocytes. Cell Biochem Funct, 23(2): 93-100

[84] Liu Y, Hao W, Dawson A, Liu S, Fassbender K (2009). Expression of amyotrophic lateral sclerosis-linked SOD1 mutant increases the neurotoxic potential of microglia via TLR2. J Biol Chem, 284(6): 3691-3699

[85] Lull M E, Levesque S, Surace M J, Block M L (2011). Chronic apocynin treatment attenuates beta amyloid plaque size and microglial number in hAPP(751)(SL) mice. PLoS ONE, 6(5): e20153

[86] Mackey A M, Sanvicens N, Groeger G, Doonan F, Wallace D, Cotter T G (2008). Redox survival signalling in retina-derived 661W cells. Cell Death Differ, 15(8): 1291-1303

[87] Malaplate-Armand C, Florent-Béchard S, Youssef I, Koziel V, Sponne I, Kriem B, Leininger-Muller B, Olivier J L, Oster T, Pillot T (2006). Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway. Neurobiol Dis, 23(1): 178-189

[88] Maldonado P D, Molina-Jijón E, Villeda-Hernández J, Galván-Arzate S, Santamaría A, Pedraza-Chaverrí J (2010). NAD(P)H oxidase contributes to neurotoxicity in an excitotoxic/prooxidant model of Huntington’s disease in rats: protective role of apocynin. J Neurosci Res, 88(3): 620-629

[89] Mander P K, Jekabsone A, Brown G C (2006). Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase. J Immunol, 176(2): 1046-1052

[90] Marden J J, Harraz M M, Williams A J, Nelson K, Luo M, Paulson H, Engelhardt J F (2007). Redox modifier genes in amyotrophic lateral sclerosis in mice. J Clin Invest, 117(10): 2913-2919

[91] Markowitz A J, White M G, Kolson D L, Jordan-Sciutto K L (2007). Cellular interplay between neurons and glia: toward a comprehensive mechanism for excitotoxic neuronal loss in neurodegeneration. Cellscience, 4(1): 111-146

[92] Martyn K D, Frederick L M, von Loehneysen K, Dinauer M C, Knaus U G (2006). Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal, 18(1): 69-82

[93] Massaad C A, Klann E (2011). Reactive oxygen species in the regulation of synaptic plasticity and memory. Antioxid Redox Signal, 14(10): 2013-2054

[94] Mizuki K, Kadomatsu K, Hata K, Ito T, Fan Q W, Kage Y, Fukumaki Y, Sakaki Y, Takeshige K, Sumimoto H (1998). Functional modules and expression of mouse p40(phox) and p67(phox), SH3-domain-containing proteins involved in the phagocyte NADPH oxidase complex. Eur J Biochem, 251(3): 573-582

[95] Morand S, Ueyama T, Tsujibe S, Saito N, Korzeniowska A, Leto T L (2009). Duox maturation factors form cell surface complexes with Duox affecting the specificity of reactive oxygen species generation. FASEB J, 23(4): 1205-1218

[96] Moreira P I, Zhu X, Wang X, Lee H G, Nunomura A, Petersen R B, Perry G, Smith M A (2010). Mitochondria: a therapeutic target in neurodegeneration. Biochim Biophys Acta, 1802(1): 212-220

[97] Munnamalai V, Suter D M (2009). Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth. J Neurochem, 108(3): 644-661

[98] Nauseef W M (2004). Assembly of the phagocyte NADPH oxidase. Histochem Cell Biol, 122(4): 277-291

[99] Nisimoto Y, Motalebi S, Han C H, Lambeth J D (1999). The p67(phox) activation domain regulates electron flow from NADPH to flavin in flavocytochrome b(558). J Biol Chem, 274(33): 22999-23005

[100] Nitti M, Furfaro A L, Cevasco C, Traverso N, Marinari U M, Pronzato M A, Domenicotti C (2010). PKC delta and NADPH oxidase in retinoic acid-induced neuroblastoma cell differentiation. Cell Signal, 22(5): 828-835

[101] Noh K M, Koh J Y (2000). Induction and activation by zinc of NADPH oxidase in cultured cortical neurons and astrocytes. J Neurosci, 20(23): RC111

[102] Ostman A, Frijhoff J, Sandin A, Böhmer F D (2011). Regulation of protein tyrosine phosphatases by reversible oxidation. J Biochem, 150(4): 345-356

[103] Pandey D, Fulton D J (2011). Molecular regulation of NADPH oxidase 5 via the MAPK pathway. Am J Physiol Heart Circ Physiol, 300(4): H1336-H1344

[104] Pandey D, Gratton J P, Rafikov R, Black S M, Fulton D J (2011). Calcium/calmodulin-dependent kinase II mediates the phosphorylation and activation of NADPH oxidase 5. Mol Pharmacol, 80(3): 407-415

[105] Pao M, Wiggs E A, Anastacio M M, Hyun J, DeCarlo E S, Miller J T, Anderson V L, Malech H L, Gallin J I, Holland S M (2004). Cognitive function in patients with chronic granulomatous disease: a preliminary report. Psychosomatics, 45(3): 230-234

[106] Park L, Zhou P, Pitstick R, Capone C, Anrather J, Norris E H, Younkin L, Younkin S, Carlson G, McEwen B S, Iadecola C (2008). Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proc Natl Acad Sci USA, 105(4): 1347-1352

[107] Parkos C A, Dinauer M C, Jesaitis A J, Orkin S H, Curnutte J T (1989). Absence of both the 91kD and 22kD subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease. Blood, 73(6): 1416-1420

[108] Pawate S, Shen Q, Fan F, Bhat N R (2004). Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J Neurosci Res, 77(4): 540-551

[109] Puntambekar P, Mukherjea D, Jajoo S, Ramkumar V (2005). Essential role of Rac1/NADPH oxidase in nerve growth factor induction of TRPV1 expression. J Neurochem, 95(6): 1689-1703

[110] Qin B, Cartier L, Dubois-Dauphin M, Li B, Serrander L, Krause K H (2006). A key role for the microglial NADPH oxidase in APP-dependent killing of neurons. Neurobiol Aging, 27(11): 1577-1587

[111] Rebola N, Srikumar B N, Mulle C (2010). Activity-dependent synaptic plasticity of NMDA receptors. J Physiol, 588(Pt 1): 93-99

[112] Reinhardt H C, Schumacher B (2012). The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet, 28(3): 128-136

[113] Rigutto S, Hoste C, Grasberger H, Milenkovic M, Communi D, Dumont J E, Corvilain B, Miot F, De Deken X (2009). Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation. J Biol Chem, 284(11): 6725-6734

[114] Roepstorff K, Rasmussen I, Sawada M, Cudre-Maroux C, Salmon P, Bokoch G, van Deurs B, Vilhardt F (2008). Stimulus-dependent regulation of the phagocyte NADPH oxidase by a VAV1, Rac1, and PAK1 signaling axis. J Biol Chem, 283(12): 7983-7993

[115] Sankarapandi S, Zweier J L, Mukherjee G, Quinn M T, Huso D L (1998). Measurement and characterization of superoxide generation in microglial cells: evidence for an NADPH oxidase-dependent pathway. Arch Biochem Biophys, 353(2): 312-321

[116] Sarfstein R, Gorzalczany Y, Mizrahi A, Berdichevsky Y, Molshanski-Mor S, Weinbaum C, Hirshberg M, Dagher M C, Pick E (2004). Dual role of Rac in the assembly of NADPH oxidase, tethering to the membrane and activation of p67phox: a study based on mutagenesis of p67phox-Rac1 chimeras. J Biol Chem, 279(16): 16007-16016

[117] Savchenko V L (2012). Regulation of NADPH oxidase gene expression with PKA and cytokine IL-4 in neurons and microglia. Neurotox Res,

[118] Sedeek M, Montezano A C, Hebert R L, Gray S P, Di Marco E, Jha J C, Cooper M E, Jandeleit-Dahm K, Schiffrin E L, Wilkinson-Berka J L, Touyz R M (2012). Oxidative stress, Nox isoforms and complications of diabetes—potential targets for novel therapies. J Cardiovasc Transl Res, 5(4): 509-518

[119] Serrano F, Kolluri N S, Wientjes F B, Card J P, Klann E (2003). NADPH oxidase immunoreactivity in the mouse brain. Brain Res, 988(1-2): 193-198

[120] Shelat P B, Chalimoniuk M, Wang J H, Strosznajder J B, Lee J C, Sun A Y, Simonyi A, Sun G Y (2008). Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J Neurochem, 106(1): 45-55

[121] Shimohama S, Tanino H, Kawakami N, Okamura N, Kodama H, Yamaguchi T, Hayakawa T, Nunomura A, Chiba S, Perry G, Smith M A, Fujimoto S (2000). Activation of NADPH oxidase in Alzheimer’s disease brains. Biochem Biophys Res Commun, 273(1): 5-9

[122] Sorce S, Krause K H, Jaquet V (2012). Targeting NOX enzymes in the central nervous system: therapeutic opportunities. Cell Mol Life Sci, 69(14): 2387-2407

[123] Stolk J, Hiltermann T J, Dijkman J H, Verhoeven A J (1994). Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am J Respir Cell Mol Biol, 11(1): 95-102

[124] Strosznajder J B, Czapski G A, Adamczyk A, Strosznajder R P (2012). Poly(ADP-ribose) polymerase-1 in amyloid beta toxicity and Alzheimer’s disease. Mol Neurobiol, 46(1): 78-84

[125] Sumimoto H, Hata K, Mizuki K, Ito T, Kage Y, Sakaki Y, Fukumaki Y, Nakamura M, Takeshige K (1996). Assembly and activation of the phagocyte NADPH oxidase. Specific interaction of the N-terminal Src homology 3 domain of p47phox with p22phox is required for activation of the NADPH oxidase. J Biol Chem, 271(36): 22152-22158

[126] Sumimoto H, Miyano K, Takeya R (2005). Molecular composition and regulation of the Nox family NAD(P)H oxidases. Biochem Biophys Res Commun, 338(1): 677-686

[127] Suzukawa K, Miura K, Mitsushita J, Resau J, Hirose K, Crystal R, Kamata T (2000). Nerve growth factor-induced neuronal differentiation requires generation of Rac1-regulated reactive oxygen species. J Biol Chem, 275(18): 13175-13178

[128] Szaingurten-Solodkin I, Hadad N, Levy R (2009). Regulatory role of cytosolic phospholipase A2alpha in NADPH oxidase activity and in inducible nitric oxide synthase induction by aggregated Abeta1-42 in microglia. Glia, 57(16): 1727-1740

[129] Tammariello S P, Quinn M T, Estus S (2000). NADPH oxidase contributes directly to oxidative stress and apoptosis in nerve growth factor-deprived sympathetic neurons. J Neurosci, 20(1): RC53

[130] Tejada-Simon M V, Serrano F, Villasana L E, Kanterewicz B I, Wu G Y, Quinn M T, Klann E (2005). Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. Mol Cell Neurosci, 29(1): 97-106

[131] Traynelis S F, Wollmuth L P, McBain C J, Menniti F S, Vance K M, Ogden K K, Hansen K B, Yuan H, Myers S J, Dingledine R (2010). Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev, 62(3): 405-496

[132] Trumbull K A, McAllister D, Gandelman M M, Fung W Y, Lew T, Brennan L, Lopez N, Morré J, Kalyanaraman B, Beckman J S (2012). Diapocynin and apocynin administration fails to significantly extend survival in G93A SOD1 ALS mice. Neurobiol Dis, 45(1): 137-144

[133] Ueno N, Takeya R, Miyano K, Kikuchi H, Sumimoto H (2005). The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J Biol Chem, 280(24): 23328-23339

[134] Verkhratsky A, Parpura V (2010). Recent advances in (patho)physiology of astroglia. Acta Pharmacol Sin, 31(9): 1044-1054

[135] Wilkinson B L, Cramer P E, Varvel N H, Reed-Geaghan E, Jiang Q, Szabo A, Herrup K, Lamb B T, Landreth G E (2012). Ibuprofen attenuates oxidative damage through NOX2 inhibition in Alzheimer’s disease. Neurobiol Aging, 33:197e21-197e32.

[136] Wu D C, Ré D B, Nagai M, Ischiropoulos H, Przedborski S (2006). The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc Natl Acad Sci USA, 103(32): 12132-12137

[137] Wu D C, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003). NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Proc Natl Acad Sci USA, 100(10): 6145-6150

[138] Zawada W M, Banninger G P, Thornton J, Marriott B, Cantu D, Rachubinski A L, Das M, Griffin W S, Jones S M (2011). Generation of reactive oxygen species in 1-methyl-4-phenylpyridinium (MPP+) treated dopaminergic neurons occurs as an NADPH oxidase-dependent two-wave cascade. J Neuroinflammation, 8(1): 129

[139] Zhang D, Hu X, Qian L, Chen S H, Zhou H, Wilson B, Miller D S, Hong J S (2011). Microglial MAC1 receptor and PI3K are essential in mediating β-amyloid peptide-induced microglial activation and subsequent neurotoxicity. J Neuroinflammation, 8(1): 3

[140] Zhang W, Wang T, Pei Z, Miller D S, Wu X, Block M L, Wilson B, Zhang W, Zhou Y, Hong J S, Zhang J (2005). Aggregated alpha-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J, 19(6): 533-542

[141] Zhou H, Zhang F, Chen S H, Zhang D, Wilson B, Hong J S, Gao H M (2012). Rotenone activates phagocyte NADPH oxidase by binding to its membrane subunit gp91phox. Free Radic Biol Med, 52(2): 303-313

[142] Zhu D, Hu C, Sheng W, Tan K S, Haidekker M A, Sun A Y, Sun G Y, Lee J C (2009). NAD(P)H oxidase-mediated reactive oxygen species production alters astrocyte membrane molecular order via phospholipase A2. Biochem J, 421(2): 201-210

[143] Zhu D, Lai Y, Shelat P B, Hu C, Sun G Y, Lee J C (2006). Phospholipases A2 mediate amyloid-beta peptide-induced mitochondrial dysfunction. J Neurosci, 26(43): 11111-11119

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