Targeting NOX enzymes in the central nervous system: Therapeutic opportunities

Cellular and Molecular Life Sciences

Volumn 69, Issue 14, 2012, Pages 2387-2407

  Sorce, Silvia ^a,b   Krause, Karl Heinz ^a,b   Jaquet, Vincent ^a,b  

^a UNIVERSITY OF GENEVA MEDICAL SCHOOL   (Switzerland)

^b GENEVA UNIVERSITY HOSPITALS   (Switzerland)

Author keywords

Alzheimer; Antioxidants; Autoimmune diseases; Brain; Central nervous system; NOX inhibitors; NOX NADPH oxidase; Oxidative stress; Parkinson; Schizophrenia; Stroke

Indexed keywords

2 ACETYLPHENOTHIAZINE; 3 PYRAZOLOPYRIDINE; ANTIOXIDANT; APOCYNIN; ATYPICAL ANTIPSYCHOTIC AGENT; BETA1A INTERFERON; CATECHOL METHYLTRANSFERASE INHIBITOR; CELASTROL; CELECOXIB; CHLORPROMAZINE; CORTICOSTEROID; DOPAMINE RECEPTOR STIMULATING AGENT; FINGOLIMOD; GLUCOCORTICOID; IMMUNOGLOBULIN; LEVODOPA; MITOXANTRONE; ML 171; MONOAMINE OXIDASE B INHIBITOR; NATALIZUMAB; NEUROLEPTIC AGENT; OXIDOREDUCTASE INHIBITOR; PERHEXILINE; PHYTOL; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; RILUZOLE; ROFECOXIB; TRIAZOLOPYRIDAZINE DERIVATIVE; UNCLASSIFIED DRUG; VAS 28701;

ALLERGIC NEUROPATHY; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANGINA PECTORIS; ANXIETY DISORDER; BRAIN HEMORRHAGE; BRAIN INFARCTION; BRAIN INJURY; BRAIN ISCHEMIA; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL EFFECTIVENESS; COGNITIVE DEFECT; DEMYELINATING DISEASE; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG EFFICACY; DRUG METABOLISM; DRUG POTENCY; DRUG SAFETY; DRUG TARGETING; DRUG TOLERABILITY; DYSKINESIA; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME MECHANISM; EPILEPSY; EXCITOTOXICITY; EXTRAPYRAMIDAL SYMPTOM; GUILLAIN BARRE SYNDROME; HUMAN; HUNTINGTON CHOREA; HYPOGLYCEMIA; METABOLIC SYNDROME X; MOLECULAR PATHOLOGY; MULTIPLE SCLEROSIS; NONHUMAN; OUTCOME ASSESSMENT; PARKINSON DISEASE; PATIENT COMPLIANCE; PLASMAPHERESIS; POSITIVE END EXPIRATORY PRESSURE; PROTEIN EXPRESSION; REVIEW; SCHIZOPHRENIA; SLEEP APNEA SYNDROME; STROKE; TREATMENT DURATION; UNSPECIFIED SIDE EFFECT;

CENTRAL NERVOUS SYSTEM DISEASES; ENZYME INHIBITORS; HUMANS; NADPH OXIDASE; PROTEIN ISOFORMS; REACTIVE OXYGEN SPECIES; SMALL MOLECULE LIBRARIES;

EID: 84864360749     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-012-1014-5     Document Type: Review

References (174)

1. Aldieri E, Riganti C, Polimeni M, Gazzano E, Lussiana C, Campia I, Ghigo D (2008) Classical inhibitors of NOX NAD(P)H oxidases are not specific. Curr Drug Metab 9:686-696
2. Aliev G, Palacios HH, Walrafen B, Lipsitt AE, Obrenovich ME, Morales L (2009) Brain mitochondria as a primary target in the development of treatment strategies for Alzheimer disease. Int J Biochem Cell Biol 41:1989-2004
3. Ansari MA, Scheff SW (2011) NADPH-oxidase activation and cognition in Alzheimer disease progression. Free Radic Biol Med 51:171-178
4. Ashrafian H, Horowitz JD, Frenneaux MP (2007) Perhexiline. Cardiovasc Drug Rev 25:76-97 (Pubitemid 46625291)
5. Barber SC, Shaw PJ (2010) Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. Free Radic Biol Med 48:629-641
6. Barten LJ, Allington DR, Procacci KA, Rivey MP (2010) New approaches in the management of multiple sclerosis. Drug Des Dev Ther 4:343-366
7. Beal MF (2002) Oxidatively modified proteins in aging and disease. Free Radic Biol Med 32:797-803 (Pubitemid 34439250)
8. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245-313 (Pubitemid 46209993)
9. Beebe DW, Gozal D (2002) Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep Res 11:1-16 (Pubitemid 34227209)
10. Beghi E, Chio A, Couratier P, Esteban J, Hardiman O, Logroscino G, Millul A, Mitchell D, Preux PM, Pupillo E, Stevic Z, Swingler R, Traynor BJ, Van den Berg LH, Veldink JH, Zoccolella S (2011) The epidemiology and treatment of ALS: focus on the heterogeneity of the disease and critical appraisal of therapeutic trials. Amyotroph Later Scler 12:1-10
11. Behrens MM, Ali SS, Dao DN, Lucero J, Shekhtman G, Quick KL, Dugan LL (2007) Ketamine-induced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science 318:1645-1647 (Pubitemid 350233667)
12. Behrens MM, Ali SS, Dugan LL (2008) Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J Neurosci 28:13957-13966
13. Behrens MM, Sejnowski TJ (2009) Does schizophrenia arise from oxidative dysregulation of parvalbumin-interneurons in the developing cortex? Neuropharmacology 57:193-200
14. Bendtzen K (2010) Critical review: assessment of interferonbeta immunogenicity in multiple sclerosis. J Interfer Cytokine Res 30:759-766
15. Bensimon A, Simon A, Chiffaudel A, Croquette V, Heslot F, Bensimon D (1994) Alignment and sensitive detection of DNA by a moving interface. Science 265:2096-2098 (Pubitemid 24325693)
16. Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI (2008) N-acetyl cysteine as a glutathione precursor for schizophrenia-a doubleblind, randomized, placebo-controlled trial. Biol Psychiatry 64:361-368
17. Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8:57-69 (Pubitemid 46011999)
18. Borbely G, Szabadkai I, Horvath Z, Marko P, Varga Z, Breza N, Baska F, Vantus T, Huszar M, Geiszt M, Hunyady L, Buday L, Orfi L, Keri G (2010) Small-molecule inhibitors of NADPH oxidase 4. J Med Chem 53:6758-6762
19. Braunersreuther V, Jaquet V (2011) Reactive Oxygen Species in Myocardial Reperfusion Injury: From Physiopathology to Therapeutic Approaches. Curr Pharm Biotechnol 13:97-114
20. Brennan AM, Suh SW, Won SJ, Narasimhan P, Kauppinen TM, Lee H, Edling Y, Chan PH, Swanson RA (2009) NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci 12:857-863
21. Briones AM, Tabet F, Callera GE, Montezano AC, Yogi A, He Y, Quinn MT, Salaices M, Touyz RM (2011) Differential regulation of Nox1, Nox2 and Nox4 in vascular smooth muscle cells from WKY and SHR. J Am Soc Hypertens 5:137-153
22. Bromet EJ, Fennig S (1999) Epidemiology and natural history of schizophrenia. Biol Psychiatry 46:871-881 (Pubitemid 29452978)
23. Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ (2002) Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients. Chest 122:1162-1167 (Pubitemid 35339525)
24. Carter MD, Simms GA, Weaver DF (2010) The development of new therapeutics for Alzheimer's disease. Clin Pharmacol Ther 88:475-486
25. Carter NJ, Keating GM (2010) Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis. Drugs70:1545-1577
26. Caslake R, Macleod A, Ives N, Stowe R, Counsell C (2009) Monoamine oxidase B inhibitors versus other dopaminergic agents in early Parkinson's disease. Cochrane Database Syst Rev: CD006661
27. Chen H, Song YS, Chan PH (2009) Inhibition of NADPH oxidase is neuroprotective after ischemia-reperfusion. J Cereb Blood Flow Metab 29:1262-1272
28. Choi DH, Cristovao AC, Guhathakurta S, Joh T, Beal F, Kim YS (2011) NADPH oxidase 1-mediated oxidative stress leads to dopamine neuron death in Parkinson's disease. Antioxid Redox Signal 16:1033-1045
29. Choi DK, Koppula S, Choi M, Suk K (2010) Recent developments in the inhibitors of neuroinflammation and neurodegeneration: inflammatory oxidative enzymes as a drug target. Expert Opin Ther Pat 20:1531-1546
30. Cleren C, Calingasan NY, Chen J, Beal MF (2005) Celastrol protects against MPTP- and 3-nitropropionic acid-induced neurotoxicity. J Neurochem 94:995-1004 (Pubitemid 41170587)
31. Cristovao AC, Choi DH, Baltazar G, Beal MF, Kim YS (2009) The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell death. Antioxid Redox Signal 11:2105-2118
32. Cui C, Chen AF, Jiang Z, Wu Q, Lin J, Wen H, Zeng J (2007) Inhibition of NAD(P)H oxidase reduces fibronectin expression in stroke-prone renovascular hypertensive rat brain. Clin Exp Pharmacol Physiol 34:304-309
33. de la Monte SM, Wands JR (2006) Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease. J Alzheimers Dis 9:167-181 (Pubitemid 44088244)
34. Dumont M, Stack C, Elipenhali C, Calingasan NY, Wille E, Beal MF (2011) Apocynin administration does not improve behavioral and neuropathological deficits in a transgenic mouse model of Alzheimer's disease. Neurosci Lett 492:150-154
35. Duty S, Jenner P (2011) Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease. Br J Pharmacol 164:1357-1391
36. Engel O, Kolodziej S, Dirnagl U, Prinz V (2011) Modeling stroke in mice-middle cerebral artery occlusion with the filament model. J Vis Exp. doi: 10.3791/2423
37. Fabian RH, Perez-Polo JR, Kent TA (2008) Perivascular nitric oxide and superoxide in neonatal cerebral hypoxia-ischemia. Am J Physiol Heart Circ Physiol 295:H1809-H1814
38. Farber NB (2003) The NMDA receptor hypofunction model of psychosis. Ann NY Acad Sci 1003:119-130 (Pubitemid 38083050)
39. Filippini G, Munari L, Incorvaia B, Ebers GC, Polman C, D'Amico R, Rice GP (2003) Interferons in relapsing remitting multiple sclerosis: a systematic review. Lancet 361:545-552 (Pubitemid 36207471)
40. Fragoso YD, Frota ER, Lopes JS, Noal JS, Giacomo MC, Gomes S, Goncalves MV, da Gama PD, Finkelsztejn A (2010) Severe depression, suicide attempts, and ideation during the use of interferon beta by patients with multiple sclerosis. Clin Neuropharmacol 33:312-316
41. Fraser PA (2011) The role of free radical generation in increasing cerebrovascular permeability. Free Radic Biol Med 51:967-977
42. Fulton DJ (2009) Nox5 and the regulation of cellular function. Antioxid Redox Signal 11:2443-2452
43. Gaggini F, Laleu B, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, Gradia A, Duboux G, Merlot C, Heitz F, Szyndralewiez C, Page P (2011) Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors. Bioorg Med Chem 19:6989-6999
44. Gatto GJ, Ao Z, Kearse MG, Zhou M, Morales CR, Daniels E, Bradley BT, Goserud MT, Goodman KB, Douglas SA, Harpel MR, Johns DG (2012) NADPH oxidase-dependent and -independent mechanisms of reported inhibitors of reactive oxygen generation. J Enzyme Inhib Med Chem (in press)
45. Genovese T, Mazzon E, Paterniti I, Esposito E, Bramanti P, Cuzzocrea S (2011) Modulation of NADPH oxidase activation in cerebral ischemia/reperfusion injury in rats.Brain Res 1372:92-102
46. Gianni D, Taulet N, Zhang H, DerMardirossian C, Kister J, Martinez L, Roush WR, Brown SJ, Bokoch GM, Rosen H (2010) A novel and specific NADPH oxidase-1 (Nox1) smallmolecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells. ACS Chem Biol 5:981-993
47. Giustarini D, Dalle-Donne I, Tsikas D, Rossi R (2009) Oxidative stress and human diseases: Origin, link, measurement, mechanisms, and biomarkers. Crit Rev Clin Lab Sci 46:241-281
48. Gold R (2011) Oral therapies for multiple sclerosis: a review of agents in phase III development or recently approved. CNS Drugs 25:37-52
49. Gordon M, Gordon AS (1981) Perhexiline maleate as a cause of reversible parkinsonism and peripheral neuropathy. J Am Geriatr Soc 29:259-262 (Pubitemid 11123030)
50. Gordon PH (2011) Amyotrophic lateral sclerosis: pathophysiology, diagnosis and management. CNS Drugs 25:1-15
51. Gupta RK, Chandra A, Verm AK, Kumar S (2010) Obstructive sleep apnoea: a clinical review. J Assoc Physicians India 58:438-441
52. Hall DJ, Han SH, Chepetan A, Inui EG, Rogers M, Dugan LL (2011) Dynamic optical imaging of metabolic and NADPH oxidase-derived superoxide in live mouse brain using fluorescence lifetime unmixing. J Cereb Blood Flow Metab 32:23-32
53. Halliday GM, Stevens CH (2011) Glia: initiators and progressors of pathology in Parkinson's disease. Mov Disord 26:6-17
54. Harraz MM, Marden JJ, Zhou W, Zhang Y, Williams A, Sharov VS, Nelson K, Luo M, Paulson H, Schoneich C, Engelhardt JF (2008) SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest 118:659-670 (Pubitemid 351206555)
55. Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4:600-609
56. Heumuller S, Wind S, Barbosa-Sicard E, Schmidt HH, Busse R, Schroder K, Brandes RP (2008) Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 51:211-217 (Pubitemid 351159930)
57. Hofstetter HH, Grau C, Buttmann M, Forsthuber TG, Gaupp S, Toyka KV, Gold R (2007) The PLPp-specific T-cell population promoted by pertussis toxin is characterized by high frequencies of IL-17-producing cells. Cytokine 40:35-43 (Pubitemid 350088499)
58. Huberle A, Beyeen AD, Ockinger J, Ayturan M, Jagodic M, de Graaf KL, Fissolo N, Marta M, Olofsson P, Hultqvist M, Holmdahl R, Olsson T, Weissert R (2009) Advanced intercross line mapping suggests that ncf1 (ean6) regulates severity in an animal model of guillain-barre syndrome. J Immunol 182:4432-4438
59. Hughes RA, Pritchard J, Hadden RD (2011) Pharmacological treatment other than corticosteroids, intravenous immunoglobulin and plasma exchange for Guillain Barre syndrome. Cochrane Database Syst Rev: CD008630
60. Hui-guo L, Kui L, Yan-ning Z, Yong-jian X (2010) Apocynin attenuate spatial learning deficits and oxidative responses to intermittent hypoxia. Sleep Med 11:205-212
61. Hultqvist M, Olofsson P, Gelderman KA, Holmberg J, Holmdahl R (2006) A new arthritis therapy with oxidative burst inducers. PLoS Med 3:e348
62. Hultqvist M, Olofsson P, Holmberg J, Backstrom BT, Tordsson J, Holmdahl R (2004) Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci USA 101:12646-12651 (Pubitemid 39122077)
63. Hultqvist M, Olsson LM, Gelderman KA, Holmdahl R (2009) The protective role of ROS in autoimmune disease. Trends Immunol 30:201-208
64. Hutchinson M (2010) Natalizumab therapy of multiple sclerosis. J Interfer Cytokine Res 30:787-789
65. Infante-Duarte C, Waiczies S, Wuerfel J, Zipp F (2008) New developments in understanding and treating neuroinflammation. J Mol Med 86:975-985
66. Jackman KA, Miller AA, De Silva TM, Crack PJ, Drummond GR, Sobey CG (2009) Reduction of cerebral infarct volume by apocynin requires pretreatment and is absent in Nox2-deficient mice. Br J Pharmacol 156:680-688
67. Jaquet V, Bedard K (2009) Editorial: Genetic mapping-the path of discovery for novel functions of the NOX NADPH oxidases. J Leukoc Biol 86:461-463
68. Jaquet V, Marcoux J, Forest E, Leidal KG, McCormick S, Westermaier Y, Perozzo R, Plastre O, Fioraso-Cartier L, Diebold B, Scapozza L, Nauseef WM, Fieschi F, Krause KH, Bedard K (2011) NOX NADPH oxidase isoforms are inhibited by celastrol with a dual mode of action. Br J Pharmacol 164:507-520
69. Jaquet V, Scapozza L, Clark R, Krause KH, Lambeth JD (2009) Small Molecule NOX Inhibitors: ROS-generating NADPH Oxidases as Therapeutic Targets. Antioxid Redox Signal 11:2535-2552
70. Kahles T, Luedike P, Endres M, Galla HJ, Steinmetz H, Busse R, Neumann-Haefelin T, Brandes RP (2007) NADPH oxidase plays a central role in blood-brain barrier damage in experimental stroke. Stroke 38:3000-3006 (Pubitemid 350035696)
71. Kane JM, Correll CU (2010) Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry 71:1115-1124
72. Kannaiyan R, Shanmugam MK, Sethi G (2011) Molecular targets of celastrol derived from Thunder of God Vine: potential role in the treatment of inflammatory disorders and cancer. Cancer Lett 303:9-20
73. Kelly KA, Li X, Tan Z, VanGilder RL, Rosen CL, Huber JD (2009) NOX2 inhibition with apocynin worsens stroke outcome in aged rats. Brain Res 1292:165-172
74. Kiaei M, Kipiani K, Petri S, Chen J, Calingasan NY, Beal MF (2005) Celastrol blocks neuronal cell death and extends life in transgenic mouse model of amyotrophic lateral sclerosis. Neurodegener Dis 2:246-254 (Pubitemid 43805908)
75. Kim JA, Neupane GP, Lee ES, Jeong BS, Park BC, Thapa P (2011) NADPH oxidase inhibitors: a patent review. Expert Opin Ther Pat 21:1148-1158
76. Kinney JW, Davis CN, Tabarean I, Conti B, Bartfai T, Behrens MM (2006) A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J Neurosci 26:1604-1615 (Pubitemid 43237031)
77. Kleinschnitz C, Grund H, Wingler K, Armitage ME, Jones E, Mittal M, Barit D, Schwarz T, Geis C, Kraft P, Barthel K, Schuhmann MK, Herrmann AM, Meuth SG, Stoll G, Meurer S, Schrewe A, Becker L, Gailus-Durner V, Fuchs H, Klopstock T, de Angelis MH, Jandeleit-Dahm K, Shah AM, Weissmann N, Schmidt HH (2010) Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. PLoS Biol 8(9). (pii: e1000479)
78. Kurz A, Perneczky R (2009) Neurobiology of cognitive disorders. Curr Opin Psychiatry 22:546-551
79. Lacomblez L, Bensimon G, Leigh PN, Guillet P, Meininger V (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 347:1425-1431 (Pubitemid 26161204)
80. Laleu B, Gaggini F, Orchard M, Fioraso-Cartier L, Cagnon L,Houngninou-Molango S, Gradia A, Duboux G, Merlot C, Heitz F, Szyndralewiez C, Page P (2010) First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J Med Chem 53:7715-7730
81. Lambeth JD, Krause KH, Clark RA (2008) NOX enzymes as novel targets for drug development. Semin Immunopathol 30:339-363
82. Lee HP, Zhu X, Casadesus G, Castellani RJ, Nunomura A, Smith MA, Lee HG, Perry G (2010) Antioxidant approaches for the treatment of Alzheimer's disease. Expert Rev Neurother 10:1201-1208
83. Leng A, Feldon J, Ferger B (2004) Long-term social isolation and medial prefrontal cortex: dopaminergic and cholinergic neurotransmission. Pharmacol Biochem Behav 77:371-379 (Pubitemid 38125171)
84. Leto TL, Morand S, Hurt D, Ueyama T (2009) Targeting and regulation of reactive oxygen species generation by Nox family NADPH oxidases. Antioxid Redox Signal 11:2607-2619
85. Levesque S, Wilson B, Gregoria V, Thorpe LB, Dallas S, Polikov VS, Hong JS, Block ML (2010) Reactive microgliosis: extracellular micro-calpain and microglia-mediated dopaminergic neurotoxicity. Brain 133:808-821
86. Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312-324 (Pubitemid 40469985)
87. Lewis DA, Lieberman JA (2000) Catching up on schizophrenia: natural history and neurobiology. Neuron 28:325-334
88. Liebeskind DS, Kasner SE (2001) Neuroprotection for ischaemic stroke: an unattainable goal? CNS Drugs 15:165-174 (Pubitemid 32281179)
89. Lincecum JM, Vieira FG, Wang MZ, Thompson K, De Zutter GS, Kidd J, Moreno A, Sanchez R, Carrion IJ, Levine BA, Al-Nakhala BM, Sullivan SM, Gill A, Perrin S (2010) From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis. Nat Genet 42:392-399
90. Liu HG, Liu K, Zhou YN, Xu YJ (2009) Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population. Chin Med J (Engl) 122:1369-1374
91. Liu W, Sood R, Chen Q, Sakoglu U, Hendren J, Cetin O, Miyake M, Liu KJ (2008) Normobaric hyperoxia inhibits NADPH oxidase-mediated matrix metalloproteinase-9 induction in cerebral microvessels in experimental stroke. J Neurochem 107:1196-1205
92. Lo A (2008) Advancement of therapies for neuroprotection in multiple sclerosis. Expert Rev Neurother 8:1355-1366
93. Lopate G, Pestronk A (2011) Inflammatory demyelinating neuropathies. Curr Treat Options Neurol 13:131-142
94. Lull ME, Block ML (2010) Microglial activation and chronic neurodegeneration. Neurotherapeutics 7:354-365
95. Lull ME, Levesque S, Surace MJ, Block ML (2011) Chronic apocynin treatment attenuates beta amyloid plaque size and microglial number in hAPP(751)(SL) mice. PLoS ONE 6:e20153
96. Maldonado PD, Molina-Jijon E, Villeda-Hernandez J, Galvan- Arzate S, Santamaria A, Pedraza-Chaverri 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 88:620-629
97. Marden JJ, Harraz MM, Williams AJ, Nelson K, Luo M, Paulson H, Engelhardt JF (2007) Redox modifier genes in amyotrophic lateral sclerosis in mice. J Clin Invest 117:2913-2919 (Pubitemid 47529621)
98. Marriott JJ, Miyasaki JM, Gronseth G, O'Connor PW (2010) Evidence Report: the efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 74:1463-1470
99. Marsh JD, Keyrouz SG (2010) Stroke prevention and treatment. J Am Coll Cardiol 56:683-691
100. Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G (2009) Mitoxantrone: benefits and risks in multiple sclerosis patients. Neurol Sci 30(Suppl 2):S167-S170
101. Masood A, Nadeem A, Mustafa SJ, O'Donnell JM (2008) Reversal of oxidative stress-induced anxiety by inhibition of phosphodiesterase-2 in mice. J Pharmacol Exp Ther 326: 369-379
102. Massaad CA, Amin SK, Hu L, Mei Y, Klann E, Pautler RG (2010) Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer's disease. PLoS ONE 5:e10561
103. Melnikova I (2007) Therapies for Alzheimer's disease. Nat Rev Drug Discov 6:341-342 (Pubitemid 46696548)
104. Miana-Mena FJ, Piedrafita E, Gonzalez-Mingot C, Larrode P, Munoz MJ, Martinez-Ballarin E, Reiter RJ, Osta R, Garcia JJ (2011) Levels of membrane fluidity in the spinal cord and the brain in an animal model of amyotrophic lateral sclerosis. J Bioenerg Biomembr 43:181-186
105. Miller RG, Mitchell JD, Lyon M, Moore DH (2003) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Amyotroph Lateral Scler Other Motor Neuron Disord 4:191-206 (Pubitemid 37184890)
106. Mitsumoto H, Santella RM, Liu X, Bogdanov M, Zipprich J, Wu HC, Mahata J, Kilty M, Bednarz K, Bell D, Gordon PH, Hornig M, Mehrazin M, Naini A, Flint Beal M, Factor-Litvak P (2008) Oxidative stress biomarkers in sporadic ALS. Amyotroph Lateral Scler 9:177-183 (Pubitemid 351983180)
107. Mohamed T, Rao PN (2011) Alzheimer's disease: emerging trends in small molecule therapies. Curr Med Chem 18:4299-4320
108. Mossberg N, Andersen O, Nilsson S, Dahlgren C, Hellstrand K, Lindh M, Svedhem A, Bergstrom T, Movitz C (2007) Oxygen radical production and severity of the Guillain-Barre syndrome. J Neuroimmunol 192:186-191 (Pubitemid 350213122)
109. Mossberg N, Andersen O, Nordin M, Nilsson S, Svedhem A, Bergstrom T, Hellstrand K, Movitz C (2010) Leukocyte oxygen radical production determines disease severity in the recurrent Guillain-Barre syndrome. J Inflamm (Lond) 7:40
110. Mossberg N, Movitz C, Hellstrand K, Bergstrom T, Nilsson S, Andersen O (2009) Oxygen radical production in leukocytes and disease severity in multiple sclerosis. J Neuroimmunol 213: 131-134
111. Murotomi K, Takagi N, Takeo S, Tanonaka K (2011) NADPH oxidase-mediated oxidative damage to proteins in the postsynaptic density after transient cerebral ischemia and reperfusion. Mol Cell Neurosci 46:681-688
112. Nair D, Dayyat EA, Zhang SX, Wang Y, Gozal D (2011) Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a murine model of sleep apnea. PLoS ONE 6:e19847
113. Nakanishi N, Tu S, Shin Y, Cui J, Kurokawa T, Zhang D, Vincent Chen H-S, Tong G, Lipton SA (2009) Neuroprotection by the NR3A subunit of the NMDA receptor. J Neurosci 29:5260-526
114. Ohlow MJ, Moosmann B (2011) Phenothiazine: the seven lives of pharmacology's first lead structure. Drug Discov Today 16:119-131
115. Ohye H, Sugawara M (2010) Dual oxidase, hydrogen peroxide and thyroid diseases. Exp Biol Med (Maywood) 235:424-433
116. Olofsson P, Holmberg J, Tordsson J, Lu S, Akerstrom B, Holmdahl R (2003) Positional identification of Ncf1 as a gene that regulates arthritis severity in rats. Nat Genet 33:25-32 (Pubitemid 36068678)
117. Palmer AM, Stephenson FA (2005) CNS drug discovery: challenges and solutions. Drug News Perspect 18:51-57 (Pubitemid 40543262)
118. Paris D, Ganey NJ, Laporte V, Patel NS, Beaulieu-Abdelahad D, Bachmeier C, March A, Ait-Ghezala G, Mullan MJ (2010) Reduction of beta-amyloid pathology by celastrol in a transgenic mouse model of Alzheimer's disease. J Neuroinflamm 7:17
119. Park L, Zhou P, Pitstick R, Capone C, Anrather J, Norris EH, Younkin L, Younkin S, Carlson G, McEwen BS, Iadecola C (2008) Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proc Natl Acad Sci USA 105:1347-1352 (Pubitemid 351397056)
120. Patten DA, Germain M, Kelly MA, Slack RS (2010) Reactive oxygen species: stuck in the middle of neurodegeneration. J Alzheimers Dis 20(Suppl 2):S357-S367
121. Perez-Lloret S, Rascol O (2010) Dopamine receptor agonists for the treatment of early or advanced Parkinson's disease. CNS Drugs 24:941-968
122. Pestana RR, Kinjo ER, Hernandes MS, Britto LR (2010) Reactive oxygen species generated by NADPH oxidase are involved in neurodegeneration in the pilocarpine model of temporal lobe epilepsy. Neurosci Lett 484:187-191
123. Peters EA, Hiltermann JT, Stolk J (2001) Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med 31:1442-1447 (Pubitemid 33145314)
124. Polymenidou M, Cleveland DW (2011) The seeds of neurodegeneration: prion-like spreading in ALS. Cell 147:498-508
125. Pozzilli C, Prosperini L, Borriello G (2010) Treating multiple sclerosis with fingolimod or intramuscular interferon. Expert Opin Pharmacother 11:1957-1960
126. Pratico D (2010) The neurobiology of isoprostanes and Alzheimer's disease. Biochim Biophys Acta 1801:930-933
127. Purisai MG, McCormack AL, Cumine S, Li J, Isla MZ, Di Monte DA (2007) Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration. Neurobiol Dis 25:392-400 (Pubitemid 46124019)
128. Qin B, Cartier L, Dubois-Dauphin M, Li B, Serrander L, Krause KH (2006) A key role for the microglial NADPH oxidase in APP-dependent killing of neurons. Neurobiol Aging 27:1577-1587 (Pubitemid 44349157)
129. Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, Liu B, Hong JS (2004) NADPH oxidase mediates lipopolysaccharideinduced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem 279:1415-1421 (Pubitemid 38082669)
130. Rappold PM, Cui M, Chesser AS, Tibbett J, Grima JC, Duan L, Sen N, Javitch JA, Tieu K (2011) Paraquat neurotoxicity is mediated by the dopamine transporter and organic cation transporter-3. Proc Natl Acad Sci USA 108:20766-20771
131. Reddy R (2011) Antioxidant Therapeutics for Schizophrenia. Antioxid Redox Signal 15:2047-2055
132. Reisberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ (2003) Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 348:1333-1341 (Pubitemid 36384100)
133. Said G (1978) Perhexiline neuropathy: a clinicopathological study. Ann Neurol 3:259-266 (Pubitemid 8364356)
134. Sanchez-Moreno C, Jimenez-Escrig A, Martin A (2009) Stroke: roles of B vitamins, homocysteine and antioxidants. Nutr Res Rev 22:49-67
135. Savitt JM, Dawson VL, Dawson TM (2006) Diagnosis and treatment of Parkinson disease: molecules to medicine. J Clin Invest 116:1744-1754 (Pubitemid 44033293)
136. Schiavone S, Sorce S, Dubois-Dauphin M, Jaquet V, Colaianna M, Zotti M, Cuomo V, Trabace L, Krause KH (2009) Involvement of NOX2 in the development of behavioral and pathologic alterations in isolated rats. Biol Psychiatry 66:384-392
137. Schulz R, Mahmoudi S, Hattar K, Sibelius U, Olschewski H, Mayer K, Seeger W, Grimminger F (2000) Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive sleep apnea. Impact of continuous positive airway pressure therapy. Am J Respir Crit Care Med 162:566-570 (Pubitemid 30647201)
138. Sedeek M, Callera G, Montezano A, Gutsol A, Heitz F, Szyndralewiez C, Page P, Kennedy CR, Burns KD, Touyz RM, Hebert RL (2010) Critical role of Nox4-based NADPH oxidase in glucose-induced oxidative stress in the kidney: implications in type 2 diabetic nephropathy. Am J Physiol Renal Physiol 299:F1348-F1358
139. Seet RC, Lee CY, Lim EC, Tan JJ, Quek AM, Chong WL, Looi WF, Huang SH, Wang H, Chan YH, Halliwell B (2010) Oxidative damage in Parkinson disease: measurement using accurate biomarkers. Free Radic Biol Med 48:560-566
140. Shimohama S, Tanino H, Kawakami N, Okamura N, Kodama H, Yamaguchi T, Hayakawa T, Nunomura A, Chiba S, Perry G, Smith MA, Fujimoto S (2000) Activation of NADPH oxidase in Alzheimer's disease brains. Biochem Biophys Res Commun 273:5-9 (Pubitemid 30426853)
141. Simonyi A, He Y, Sheng W, Sun AY, Wood WG, Weisman GA, Sun GY (2010) Targeting NADPH oxidase and phospholipases A2 in Alzheimer's disease. Mol Neurobiol 41:73-86
142. Sorce S, Krause KH (2009) NOX enzymes in the central nervous system: from signaling to disease. Antioxid Redox Signal 11:2481-2504
143. Sorce S, Schiavone S, Tucci P, Colaianna M, Jaquet V, Cuomo V, Dubois-Dauphin M, Trabace L, Krause KH (2010) The NADPH oxidase NOX2 controls glutamate release: a novel mechanism involved in psychosis-like ketamine responses. J Neurosci 30:11317-11325
144. Stefanska J, Pawliczak R (2008) Apocynin: molecular aptitudes. Mediat Inflamm 2008:106507
145. Stolk J, Hiltermann TJ, Dijkman JH, Verhoeven AJ (1994) Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am J Respir Cell Mol Biol 11:95-102
146. Sudeshna G, Parimal K (2010) Multiple non-psychiatric effects of phenothiazines: a review. Eur J Pharmacol 648:6-14
147. Suh SW, Gum ET, Hamby AM, Chan PH, Swanson RA (2007) Hypoglycemic neuronal death is triggered by glucose reperfusion and activation of neuronal NADPH oxidase. J Clin Invest 117:910-918 (Pubitemid 46556747)
148. Suh SW, Shin BS, Ma H, Van Hoecke M, Brennan AM, Yenari MA, Swanson RA (2008) Glucose and NADPH oxidase drive neuronal superoxide formation in stroke. Ann Neurol 64: 654-663
149. Tang LL, Ye K, Yang XF, Zheng JS (2007) Apocynin attenuates cerebral infarction after transient focal ischaemia in rats. J Int Med Res 35:517-522 (Pubitemid 47261114)
150. Tang XN, Cairns B, Cairns N, Yenari MA (2008) Apocynin improves outcome in experimental stroke with a narrow dose range. Neuroscience 154:556-562
151. Titova E, Ostrowski RP, Sowers LC, Zhang JH, Tang J (2007) Effects of apocynin and ethanol on intracerebral haemorrhage-induced brain injury in rats. Clin Exp Pharmacol Physiol 34:845-850 (Pubitemid 47083966)
152. Trumbull KA, McAllister D, Gandelman MM, Fung WY, Lew T, Brennan L, Lopez N, Morre J, Kalyanaraman B, Beckman JS (2012) Diapocynin and apocynin administration fails to significantly extend survival in G93A SOD1 ALS mice. Neurobiol Dis 45:137-144
153. van Horssen J, Witte ME, Schreibelt G, de Vries HE (2011) Radical changes in multiple sclerosis pathogenesis. Biochim Biophys Acta 1812:141-150
154. Vendrov AE, Madamanchi NR, Niu XL, Molnar KC, Runge M, Szyndralewiez C, Page P, Runge MS (2010) NADPH oxidases regulate CD44 and hyaluronic acid expression in thrombintreated vascular smooth muscle cells and in atherosclerosis. J Biol Chem 285:26545-26557
155. Violi F, Sanguigni V, Carnevale R, Plebani A, Rossi P, Finocchi A, Pignata C, De Mattia D, Martire B, Pietrogrande MC, Martino S, Gambineri E, Soresina AR, Pignatelli P, Martino F, Basili S, Loffredo L (2009) Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study. Circulation 120:1616-1622
156. Violi F, Sanguigni V, Loffredo L, Carnevale R, Buchetti B, Finocchi A, Tesauro M, Rossi P, Pignatelli P (2006) Nox2 is determinant for ischemia-induced oxidative stress and arterial vasodilatation: a pilot study in patients with hereditary Nox2 deficiency. Arterioscler Thromb Vasc Biol 26:e131-e132 (Pubitemid 44305354)
157. Walder CE, Green SP, Darbonne WC, Mathias J, Rae J, Dinauer MC, Curnutte JT, Thomas GR (1997) Ischemic stroke injury is reduced in mice lacking a functional NADPH oxidase. Stroke 28:2252-2258 (Pubitemid 27497931)
158. Wan Y, Xu J, Meng F, Bao Y, Ge Y, Lobo N, Vizcaychipi MP, Zhang D, Gentleman SM, Maze M, Ma D (2010) Cognitive decline following major surgery is associated with gliosis, betaamyloid accumulation, and tau phosphorylation in old mice. Crit Care Med 38:2190-2198
159. Wang Q, Smith RE, Luchtefeld R, Sun AY, Simonyi A, Luo R, Sun GY (2008) Bioavailability of apocynin through its conversion to glycoconjugate but not to diapocynin. Phytomedicine 15:496-503 (Pubitemid 351790760)
160. Wang Q, Tompkins KD, Simonyi A, Korthuis RJ, Sun AY, Sun GY (2006) Apocynin protects against global cerebral ischemiareperfusion-induced oxidative
161. Wang Y, Zhang SX, Gozal D (2010) Reactive oxygen species and the brain in sleep apnea. Respir Physiol Neurobiol 174:307-316
162. Wind S, Beuerlein K, Eucker T, Muller H, Scheurer P, Armitage ME, Ho H, Schmidt HH, Wingler K (2010) Comparative pharmacology of chemically distinct NADPH oxidase inhibitors. Br J Pharmacol 161:885-898
163. Wipfler P, Harrer A, Pilz G, Oppermann K, Trinka E, Kraus J (2011) Recent developments in approved and oral multiple sclerosis treatment and an update on future treatment options. Drug Discov Today 16:8-21
164. Wu DC, Re DB, 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 103:12132-12137 (Pubitemid 44215823)
165. Xian NT, Zhen Z, Rona GG, Midori AY (2011) Significance of marrow derived NADPH oxidase in experimental ischemic stroke. Ann Neurol 70:606-615
166. Yamamoto E, Tamamaki N, Nakamura T, KataokaK, TokutomiY, Dong YF, Fukuda M, Matsuba S, Ogawa H, Kim-Mitsuyama S (2008) Excess salt causes cerebral neuronal apoptosis and inflammation in stroke-prone hypertensive rats through angiotensin II-induced NADPH oxidase activation. Stroke 39:3049-3056
167. Yoshioka H, Niizuma K, Katsu M, Okami N, Sakata H, Kim GS, Narasimhan P, Chan PH (2011) NADPH oxidase mediates striatal neuronal injury after transient global cerebral ischemia. J Cereb Blood Flow Metab 31:868-880
168. Zamvil SS, Steinman L (1990) The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol 8:579-621 (Pubitemid 20135640)
169. Zhan G, Serrano F, Fenik P, Hsu R, Kong L, Pratico D, Klann E, Veasey SC (2005) NADPH oxidase mediates hypersomnolence and brain oxidative injury in a murine model of sleep apnea. Am J Respir Crit Care Med 172:921-929 (Pubitemid 41369078)
170. Zhang W, Wang T, Qin L, Gao HM, Wilson B, Ali SF, Hong JS, Liu B (2004) Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase. FASEB J 18:589-591
171. Zhao H, Mayhan WG, Arrick DM, Xiong W, Sun H (2010) Alcohol-induced exacerbation of ischemic brain injury: role of NAD(P)H oxidase. Alcohol Clin Exp Res 34:1948-1955
172. Zheng JS, Zhan RY, Zheng SS, Zhou YQ, Tong Y, Wan S (2005) Inhibition of NADPH oxidase attenuates vasospasm after experimental subarachnoid hemorrhage in rats. Stroke 36:1059-1064
173. Zhu Y, Fenik P, Zhan G, Mazza E, Kelz M, Aston-Jones G, Veasey SC (2007) Selective loss of catecholaminergic wake active neurons in a murine sleep apnea model. J Neurosci 27:10060-10071 (Pubitemid 47404016)
174. Zia MT, Csiszar A, Labinskyy N, Hu F, Vinukonda G, LaGamma EF, Ungvari Z, Ballabh P (2009) Oxidative-nitrosative stress in a rabbit pup model of germinal matrix hemorrhage: role of NAD(P)H oxidase. Stroke 40:2191-2198