Oxidative stress, neuroinflammation, and neurodegeneration

Neuroinflammation and Neurodegeneration

Volumn , Issue , 2014, Pages 81-104

  Gao, Hui Ming ^a,b   Zhou, Hui ^b   Hong, Jau Shyong ^b  

^a NANJING UNIVERSITY   (China)

^b NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

Antioxidant; Microglia; Mitochondria; NADPH oxidase; Neurodegenerative diseases; Neuroinflammation; Neuroprotection; Oxidative stress; Reactive oxygen species

Indexed keywords

EID: 84929925778     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4939-1071-7_5     Document Type: Chapter

References (149)

1. Barnham KJ, Masters CL, Bush AI. Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov. 2004;3:205-14.
2. Zhou C, Huang Y, Przedborski S. Oxidative stress in Parkinson's disease: A mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci. 2008;1147:93-104.
3. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245-313.
4. Sorce S, Krause KH. NOX enzymes in the central nervous system: from signaling to disease. Antioxid Redox Signal. 2009;11:2481-504.
5. Smythies JR. Oxidative reactions and schizophrenia: A review-discussion. Schizophr Res. 1997;24:357-64.
6. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science. 1993;262:689-95.
7. Youdim MB, Stephenson G, Ben Shachar D. Ironing iron out in Parkinson's disease and other neurodegenerative diseases with iron chelators: A lesson from 6-hydroxydopamine and iron chelators, desferal and VK-28. Ann N Y Acad Sci. 2004;1012:306-25.
8. Kvaltinova Z, Lukovic L, Stolc S. Effect of incomplete ischemia and reperfusion of the rat brain on the density and affinity of alpha-adrenergic binding sites in the cerebral cortex. Prevention of changes by stobadine and vitamin E. Neuropharmacology. 1993;32:785-91.
9. Joseph JA, Denisova N, Fisher D, Shukitt-Hale B, Bickford P, Prior R, Cao G. Membrane and receptor modifications of oxidative stress vulnerability in aging. Nutritional considerations. Ann N Y Acad Sci. 1998;854:268-76.
10. Sah R, GaleffiF, Ahrens R, Jordan G, Schwartz-Bloom RD. Modulation of the GABA(A)-gated chloride channel by reactive oxygen species. J Neurochem. 2002;80:383-91.
11. Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787-95.
12. Abramov AY, Canevari L, Duchen MR. Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci. 2004;24:565-75.
13. Goodwin J, Nath S, Engelborghs Y, Pountney DL. Raised calcium and oxidative stress cooperatively promote alpha-synuclein aggregate formation. Neurochem Int. 2013;62:703-11.
14. Chen L, Xu B, Liu L, Luo Y, Zhou H, Chen W, Shen T, Han X, Kontos CD, Huang S. Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radic Biol Med. 2011;50:624-32.
15. Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J Neurochem. 2002;81:1285-97.
16. Marklund SL, Westman NG, Lundgren E, Roos G. Copper-and zinc-containing superoxide dismutase, manganese-containing superoxide dismutase, catalase, and glutathione peroxidase in normal and neoplastic human cell lines and normal human tissues. Cancer Res. 1982;42:1955-61.
17. Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552:335-44.
18. Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem. 2005;12:1161-208.
19. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279:L1005-28.
20. Dasuri K, Zhang L, Keller JN. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic Biol Med. 2013;62:170-85.
21. Gao HM, Zhang F, Zhou H, Kam W, Wilson B, Hong JS. Neuroinflammation and alphasynuclein dysfunction potentiate each other, driving chronic progression of neurodegeneration in a mouse model of Parkinson's disease. Environ Health Perspect. 2011;119:807-14.
22. Cheng G, Lambeth JD. NOXO1, regulation of lipid binding, localization, and activation of Nox1 by the Phox homology (PX) domain. J Biol Chem. 2004;279:4737-42.
23. Valente AJ, El Jamali A, Epperson TK, Gamez MJ, Pearson DW, Clark RA. NOX1 NADPH oxidase regulation by the NOXA1 SH3 domain. Free Radic Biol Med. 2007;43:384-96.
24. Cheng G, Ritsick D, Lambeth JD. Nox3 regulation by NOXO1, p47phox, and p67phox. J Biol Chem. 2004;279:34250-5.
25. Ueno N, Takeya R, Miyano K, Kikuchi H, Sumimoto H. The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J Biol Chem. 2005;280:23328-39.
26. Babior BM. NADPH oxidase. Curr Opin Immunol. 2004;16:42-7.
27. Gao HM, Zhou H, Hong JS. NADPH oxidases: novel therapeutic targets for neurodegenerative diseases. Trends Pharmacol Sci. 2012;33:295-303.
28. Mander PK, Jekabsone A, Brown GC. Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase. J Immunol. 2006;176:1046-52.
29. Harrigan TJ, Abdullaev IF, Jourd'heuil D, Mongin AA. Activation of microglia with zymosan promotes excitatory amino acid release via volume-regulated anion channels: The role of NADPH oxidases. J Neurochem. 2008;106:2449-62.
30. Barger SW, Goodwin ME, Porter MM, Beggs ML. Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation. J Neurochem. 2007;101:1205-13.
31. Marin-Teva JL, Dusart I, Colin C, Gervais A, van Rooijen N, Mallat M. Microglia promote the death of developing Purkinje cells. Neuron. 2004;41:535-47.
32. Ibi M, Katsuyama M, Fan C, Iwata K, Nishinaka T, Yokoyama T, Yabe-Nishimura C. NOX1/ NADPH oxidase negatively regulates nerve growth factor-induced neurite outgrowth. Free Radic Biol Med. 2006;40:1785-95.
33. Munnamalai V, Suter DM. Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth. J Neurochem. 2009;108:644-61.
34. Zimmerman MC, Dunlay RP, Lazartigues E, Zhang Y, Sharma RV, Engelhardt JF, Davisson RL. Requirement for Rac1-dependent NADPH oxidase in the cardiovascular and dipsogenic actions of angiotensin II in the brain. Circ Res. 2004;95:532-9.
35. Wang G, Anrather J, Huang J, Speth RC, Pickel VM, Iadecola C. NADPH oxidase contributes to angiotensin II signaling in the nucleus tractus solitarius. J Neurosci. 2004;24:5516-24.
36. Abramov AY, Jacobson J, Wientjes F, Hothersall J, Canevari L, Duchen MR. Expression and modulation of an NADPH oxidase in mammalian astrocytes. J Neurosci. 2005;25:9176-84.
37. Pao M, Wiggs EA, Anastacio MM, Hyun J, DeCarlo ES, Miller JT, Anderson VL, Malech HL, Gallin JI, Holland SM. Cognitive function in patients with chronic granulomatous disease: A preliminary report. Psychosomatics. 2004;45:230-4.
38. Kishida KT, Hoeffer CA, Hu D, Pao M, Holland SM, Klann E. Synaptic plasticity deficits and mild memory impairments in mouse models of chronic granulomatous disease. Mol Cell Biol. 2006;26:5908-20.
39. Ansari MA, Scheff SW. NADPH-oxidase activation and cognition in Alzheimer disease progression. Free Radic Biol Med. 2011;51:171-8.
40. Shimohama S, Tanino H, Kawakami N, Okamura N, Kodama H, Yamaguchi T, Hayakawa T, Nunomura A, Chiba S, Perry G, Smith MA, Fujimoto S. Activation of NADPH oxidase in Alzheimer's disease brains. Biochem Biophys Res Commun. 2000;273:5-9.
41. de la Monte SM, Wands JR. Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease. J Alzheimers Dis. 2006;9:167-81.
42. Vallet P, Charnay Y, Steger K, Ogier-Denis E, Kovari E, Herrmann F, Michel JP, Szanto I. Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia. Neuroscience. 2005;132:233-8.
43. Anantharam V, Kaul S, Song C, Kanthasamy A, Kanthasamy AG. Pharmacological inhibition of neuronal NADPH oxidase protects against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress and apoptosis in mesencephalic dopaminergic neuronal cells. Neurotoxicology. 2007;28:988-97.
44. Cristovao AC, Choi DH, Baltazar G, Beal MF, Kim YS. The role of NADPH oxidase 1-derived reactive oxygen species in paraquat-mediated dopaminergic cell death. Antioxid Redox Signal. 2009;11:2105-18.
45. Cheret C, Gervais A, Lelli A, Colin C, Amar L, Ravassard P, Mallet J, Cumano A, Krause KH, Mallat M. Neurotoxic activation of microglia is promoted by a nox1-dependent NADPH oxidase. J Neurosci. 2008;28:12039-51.
46. Marden JJ, Harraz MM, Williams AJ, Nelson K, Luo M, Paulson H, Engelhardt JF. Redox modifier genes in amyotrophic lateral sclerosis in mice. J Clin Invest. 2007;117:2913-9.
47. del Rio LA, Sandalio LM, Palma JM, Bueno P, Corpas FJ. Metabolism of oxygen radicals in peroxisomes and cellular implications. Free Radic Biol Med. 1992;13:557-80.
48. Recuero M, Vicente MC, Martinez-Garcia A, Ramos MC, Carmona-Saez P, Sastre I, Aldudo J, Vilella E, Frank A, Bullido MJ, Valdivieso F. A free radical-generating system induces the cholesterol biosynthesis pathway: A role in Alzheimer's disease. Aging Cell. 2009;8:128-39.
49. Dykens JA, Stern A, Trenkner E. Mechanism of kainate toxicity to cerebellar neurons in vitro is analogous to reperfusion tissue injury. J Neurochem. 1987;49:1222-8.
50. Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev. 2002;54:271-84.
51. Liu B, Gao HM, Wang JY, Jeohn GH, Cooper CL, Hong JS. Role of nitric oxide in inflammation-mediated neurodegeneration. Ann N Y Acad Sci. 2002;962:318-31.
52. Uehara T, Nakamura T, Yao D, Shi ZQ, Gu Z, Ma Y, Masliah E, Nomura Y, Lipton SA. S-nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration. Nature. 2006;441:513-7.
53. Yao D, Gu Z, Nakamura T, Shi ZQ, Ma Y, Gaston B, Palmer LA, Rockenstein EM, Zhang Z, Masliah E, Uehara T, Lipton SA. Nitrosative stress linked to sporadic Parkinson's disease: S-nitrosylation of parkin regulates its E3 ubiquitin ligase activity. Proc Natl Acad Sci U S A. 2004;101:10810-4.
54. Cho DH, Nakamura T, Fang J, Cieplak P, Godzik A, Gu Z, Lipton SA. S-nitrosylation of Drp1 mediates beta-amyloid-related mitochondrialfission and neuronal injury. Science. 2009;324:102-5.
55. Schonhoff CM, Matsuoka M, Tummala H, Johnson MA, Estevez AG, Wu R, Kamaid A, Ricart KC, Hashimoto Y, Gaston B, Macdonald TL, Xu Z, Mannick JB. S-nitrosothiol depletion in amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2006;103:2404-9.
56. Harraz MM, Marden JJ, Zhou W, Zhang Y, Williams A, Sharov VS, Nelson K, Luo M, Paulson H, Schoneich C, Engelhardt JF. SOD1 mutations disrupt redox-sensitive Rac regulation of NADPH oxidase in a familial ALS model. J Clin Invest. 2008;118:659-70.
57. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, Kassiotis G, Kollias G, Cleveland DW. Onset and progression in inherited ALS determined by motor neurons and microglia. Science. 2006;312:1389-92.
58. Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, Maier CM, Narasimhan P, Goeders CE, Chan PH. Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal. 2011;14:1505-17.
59. Jung JE, Kim GS, Narasimhan P, Song YS, Chan PH. Regulation of Mn-superoxide dismutase activity and neuroprotection by STAT3 in mice after cerebral ischemia. J Neurosci. 2009;29:7003-14.
60. Yang G, Chan PH, Chen J, Carlson E, Chen SF, Weinstein P, Epstein CJ, Kamii H. Human copper-zinc superoxide dismutase transgenic mice are highly resistant to reperfusion injury after focal cerebral ischemia. Stroke. 1994;25:165-70.
61. Murakami K, Kondo T, Epstein CJ, Chan PH. Overexpression of CuZn-superoxide dismutase reduces hippocampal injury after global ischemia in transgenic mice. Stroke. 1997;28: 1797-804.
62. Keller JN, Kindy MS, Holtsberg FW, St Clair DK, Yen HC, Germeyer A, Steiner SM, Bruce-Keller AJ, Hutchins JB, Mattson MP. Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J Neurosci. 1998;18:687-97.
63. Lee BI, Chan PH, Kim GW. Metalloporphyrin-based superoxide dismutase mimic attenuates the nuclear translocation of apoptosis-inducing factor and the subsequent DNA fragmentation after permanent focal cerebral ischemia in mice. Stroke. 2005;36:2712-7.
64. Kondo T, Reaume AG, Huang TT, Carlson E, Murakami K, Chen SF, Hoffman EK, Scott RW, Epstein CJ, Chan PH. Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia. J Neurosci. 1997;17:4180-9.
65. Murakami K, Murata N, Noda Y, Tahara S, Kaneko T, Kinoshita N, Hatsuta H, Murayama S, Barnham KJ, Irie K, Shirasawa T, Shimizu T. SOD1 (copper/zinc superoxide dismutase) deficiency drives amyloid beta protein oligomerization and memory loss in mouse model of Alzheimer disease. J Biol Chem. 2011;286:44557-68.
66. Esposito L, Raber J, Kekonius L, Yan F, Yu GQ, Bien-Ly N, Puolivali J, Scearce-Levie K, Masliah E, Mucke L. Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in human amyloid precursor protein transgenic mice. J Neurosci. 2006;26:5167-79.
67. Mao P, Manczak M, Calkins MJ, Truong Q, Reddy TP, Reddy AP, Shirendeb U, Lo HH, Rabinovitch PS, Reddy PH. Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension. Hum Mol Genet. 2012;21:2973-90.
68. Kim SO, Cho IS, Gu HK, Lee DH, Lim H, Yoo SE. KR-31378 protects neurons from ischemia-reperfusion brain injury by attenuating lipid peroxidation and glutathione loss. Eur J Pharmacol. 2004;487:81-91.
69. Martin HL, Teismann P. Glutathione-A review on its role and significance in Parkinson's disease. FASEB J. 2009;23:3263-72.
70. Klivenyi P, Andreassen OA, Ferrante RJ, Dedeoglu A, Mueller G, Lancelot E, Bogdanov M, Andersen JK, Jiang D, Beal MF. Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. J Neurosci. 2000;20:1-7.
71. Poole LB. Bacterial defenses against oxidants: mechanistic features of cysteine-based peroxidases and theirflavoprotein reductases. Arch Biochem Biophys. 2005;433:240-54.
72. Gan Y, Ji X, Hu X, Luo Y, Zhang L, Li P, Liu X, Yan F, Vosler P, Gao Y, Stetler RA, Chen J. Transgenic overexpression of peroxiredoxin-2 attenuates ischemic neuronal injury via suppression of a redox-sensitive pro-death signaling pathway. Antioxid Redox Signal. 2012;17:719-32.
73. Hu X, Weng Z, Chu CT, Zhang L, Cao G, Gao Y, Signore A, Zhu J, Hastings T, Greenamyre JT, Chen J. Peroxiredoxin-2 protects against 6-hydroxydopamine-induced dopaminergic neurodegeneration via attenuation of the apoptosis signal-regulating kinase (ASK1) signaling cascade. J Neurosci. 2011;31:247-61.
74. Hyun DH, Emerson SS, Jo DG, Mattson MP, de Cabo R. Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging. Proc Natl Acad Sci U S A. 2006;103:19908-12.
75. Hyun DH, Mughal MR, Yang H, Lee JH, Ko EJ, Hunt ND, de Cabo R, Mattson MP. The plasma membrane redox system is impaired by amyloid beta-peptide and in the hippocampus and cerebral cortex of 3xTgAD mice. Exp Neurol. 2010;225:423-9.
76. Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7:65-74.
77. Ouahchi K, Arita M, Kayden H, Hentati F, Ben Hamida M, Sokol R, Arai H, Inoue K, Mandel JL, Koenig M. Ataxia with isolated vitamin E deficiency is caused by mutations in the alphatocopherol transfer protein. Nat Genet. 1995;9:141-5.
78. Dunnett SB, Bjorklund A. Prospects for new restorative and neuroprotective treatments in Parkinson's disease. Nature. 1999;399:A32-9.
79. Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004;10(Suppl):S18-25.
80. Spindler M, Beal MF, Henchcliffe C. Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat. 2009;5:597-610.
81. Beal MF. Bioenergetic approaches for neuroprotection in Parkinson's disease. Ann Neurol. 2003;53 Suppl 3:S39-47. discussion S47-38.
82. Beal MF. A phase III clinical trial of coenzyme Q10 (QE3) in early Parkinson's disease: Parkinson Study Group QE3 Investigators [meeting abstract]. Mov Disord. 2012;27:346.
83. Masutani H, Bai J, Kim YC, Yodoi J. Thioredoxin as a neurotrophic cofactor and an important regulator of neuroprotection. Mol Neurobiol. 2004;29:229-42.
84. Umeda-Kameyama Y, Tsuda M, Ohkura C, Matsuo T, Namba Y, Ohuchi Y, Aigaki T. Thioredoxin suppresses Parkin-associated endothelin receptor-like receptor-induced neurotoxicity and extends longevity in Drosophila. J Biol Chem. 2007;282:11180-7.
85. Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA. Gene regulation and DNA damage in the ageing human brain. Nature. 2004;429:883-91.
86. Perry G, Cash AD, Smith MA. Alzheimer Disease and Oxidative Stress. J Biomed Biotechnol. 2002;2:120-3.
87. Mecocci P, MacGarvey U, Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol. 1994;36:747-51.
88. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci U S A. 1994;91:10771-8.
89. Busciglio J, Pelsman A, Wong C, Pigino G, Yuan M, Mori H, Yankner BA. Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down's syndrome. Neuron. 2002;33:677-88.
90. Li F, Calingasan NY, Yu F, Mauck WM, Toidze M, Almeida CG, Takahashi RH, Carlson GA, Flint Beal M, Lin MT, Gouras GK. Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. J Neurochem. 2004;89:1308-12.
91. Keeney PM, Xie J, Capaldi RA, Bennett Jr JP. Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 2006;26:5256-64.
92. Gao HM, Hong JS. Gene-environment interactions: key to unraveling the mystery of Parkinson's disease. Prog Neurobiol. 2011;94:1-19.
93. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD. Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem. 1990;54:823-7.
94. Castello PR, Drechsel DA, Patel M. Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem. 2007;282:14186-93.
95. Schapira AH. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol. 2008;7:97-109.
96. Gao HM, Kotzbauer PT, Uryu K, Leight S, Trojanowski JQ, Lee VM. Neuroinflammation and oxidation/nitration of alpha-synuclein linked to dopaminergic neurodegeneration. J Neurosci. 2008;28:7687-98.
97. Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK. Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem. 2008;283:9089-100.
98. Martin LJ, Pan Y, Price AC, Sterling W, Copeland NG, Jenkins NA, Price DL, Lee MK. Parkinson's disease alpha-synuclein transgenic mice develop neuronal mitochondrial degeneration and cell death. J Neurosci. 2006;26:41-50.
99. Willis CL, Ray DE. Antioxidants attenuate MK-801-induced cortical neurotoxicity in the rat. Neurotoxicology. 2007;28:161-7.
100. Brennan AM, Suh SW, Won SJ, Narasimhan P, Kauppinen TM, Lee H, Edling Y, Chan PH, Swanson RA. NADPH oxidase is the primary source of superoxide induced by NMDA receptor activation. Nat Neurosci. 2009;12:857-63.
101. Girouard H, Wang G, Gallo EF, Anrather J, Zhou P, Pickel VM, Iadecola C. NMDA receptor activation increases free radical production through nitric oxide and NOX2. J Neurosci. 2009;29:2545-52.
102. Behrens MM, Ali SS, Dao DN, Lucero J, Shekhtman G, Quick KL, Dugan LL. Ketamineinduced loss of phenotype of fast-spiking interneurons is mediated by NADPH-oxidase. Science. 2007;318:1645-7.
103. Behrens MM, Ali SS, Dugan LL. Interleukin-6 mediates the increase in NADPH-oxidase in the ketamine model of schizophrenia. J Neurosci. 2008;28:13957-66.
104. Ha JS, Lim HM, Park SS. Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity. Brain Res. 2010;1359:291-7.
105. Gao HM, Hong JS. Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol. 2008;29:357-65.
106. Philips T, Robberecht W. Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease. Lancet Neurol. 2011;10:253-63.
107. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140:918-34.
108. Milton RH, Abeti R, Averaimo S, DeBiasi S, Vitellaro L, Jiang L, Curmi PM, Breit SN, Duchen MR, Mazzanti M. CLIC1 function is required for beta-amyloid-induced generation of reactive oxygen species by microglia. J Neurosci. 2008;28:11488-99.
109. Wilkinson B, Koenigsknecht-Talboo J, Grommes C, Lee CY, Landreth G. Fibrillar betaamyloid-stimulated intracellular signaling cascades require Vav for induction of respiratory burst and phagocytosis in monocytes and microglia. J Biol Chem. 2006;281:20842-50.
110. Kim JS, Diebold BA, Babior BM, Knaus UG, Bokoch GM. Regulation of Nox1 activity via protein kinase A-mediated phosphorylation of NoxA1 and 14-3-3 binding. J Biol Chem. 2007;282:34787-800.
111. Parvathenani LK, Tertyshnikova S, Greco CR, Roberts SB, Robertson B, Posmantur R. P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. J Biol Chem. 2003;278:13309-17.
112. Choi DY, Lee MK, Hong JT. Lack of CCR5 modifies glial phenotypes and population of the nigral dopaminergic neurons, but not MPTP-induced dopaminergic neurodegeneration. Neurobiol Dis. 2012;49C:159-68.
113. Qin L, Liu Y, Cooper C, Liu B, Wilson B, Hong JS. Microglia enhance beta-amyloid peptideinduced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species. J Neurochem. 2002;83:973-83.
114. Qin B, Cartier L, Dubois-Dauphin M, Li B, Serrander L, Krause KH. A key role for the microglial NADPH oxidase in APP-dependent killing of neurons. Neurobiol Aging. 2006;27:1577-87.
115. Park L, Zhou P, Pitstick R, Capone C, Anrather J, Norris EH, Younkin L, Younkin S, Carlson G, McEwen BS, Iadecola C. Nox2-derived radicals contribute to neurovascular and behavioral dysfunction in mice overexpressing the amyloid precursor protein. Proc Natl Acad Sci U S A. 2008;105:1347-52.
116. Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S. 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 U S A. 2003;100:6145-50.
117. Gao HM, Hong JS, Zhang W, Liu B. Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. J Neurosci. 2003;23:1228-36.
118. Gao HM, Liu B, Hong JS. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci. 2003;23:6181-7.
119. Gao HM, Liu B, Zhang W, Hong JS. Critical role of microglial NADPH oxidase-derived free radicals in the in vitro MPTP model of Parkinson's disease. FASEB J. 2003;17:1954-6.
120. Qin L, Liu Y, Wang T, Wei SJ, Block ML, Wilson B, Liu B, Hong JS. NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem. 2004;279:1415-21.
121. Rodriguez-Pallares J, Parga JA, Munoz A, Rey P, Guerra MJ, Labandeira-Garcia JL. Mechanism of 6-hydroxydopamine neurotoxicity: The role of NADPH oxidase and microglial activation in 6-hydroxydopamine-induced degeneration of dopaminergic neurons. J Neurochem. 2007;103:145-56.
122. Rodriguez-Pallares J, Rey P, Parga JA, Munoz A, Guerra MJ, Labandeira-Garcia JL. Brain angiotensin enhances dopaminergic cell death via microglial activation and NADPH-derived ROS. Neurobiol Dis. 2008;31:58-73.
123. Wu XF, Block ML, Zhang W, Qin L, Wilson B, Zhang WQ, Veronesi B, Hong JS. The role of microglia in paraquat-induced dopaminergic neurotoxicity. Antioxid Redox Signal. 2005;7:654-61.
124. Block ML, Wu X, Pei Z, Li G, Wang T, Qin L, Wilson B, Yang J, Hong JS, Veronesi B. Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: The role of microglia, phagocytosis, and NADPH oxidase. FASEB J. 2004;18:1618-20.
125. Gao X, Hu X, Qian L, Yang S, Zhang W, Zhang D, Wu X, Fraser A, Wilson B, Flood PM, Block M, Hong JS. Formyl-methionyl-leucyl-phenylalanine-induced dopaminergic neurotoxicity via microglial activation: A mediator between peripheral infection and neurodegeneration? Environ Health Perspect. 2008;116:593-8.
126. Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhou Y, Hong JS, Zhang J. Aggregated alpha-synuclein activates microglia: A process leading to disease progression in Parkinson's disease. FASEB J. 2005;19:533-42.
127. Kim YS, Choi DH, Block ML, Lorenzl S, Yang L, Kim YJ, Sugama S, Cho BP, Hwang O, Browne SE, Kim SY, Hong JS, Beal MF, Joh TH. A pivotal role of matrix metalloproteinase-3 activity in dopaminergic neuronal degeneration via microglial activation. FASEB J. 2007;21:179-87.
128. Gao HM, Zhou H, Zhang F, Wilson BC, Kam W, Hong JS. HMGB1 acts on microglia Mac1 to mediate chronic neuroinflammation that drives progressive neurodegeneration. J Neurosci. 2011;31:1081-92.
129. Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci. 2002;22:1763-71.
130. Zhang W, Wang T, Qin L, Gao HM, Wilson B, Ali SF, Hong JS, Liu B. Neuroprotective effect of dextromethorphan in the MPTP Parkinson's disease model: role of NADPH oxidase. FASEB J. 2004;18:589-91.
131. Wu DC, Re DB, Nagai M, Ischiropoulos H, Przedborski S. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc Natl Acad Sci U S A. 2006;103:12132-7.
132. Li Q, Spencer NY, Pantazis NJ, Engelhardt JF. ALSIN and SOD1G93A regulate endosomal ROS production by glial cells and pro-inflammatory pathways responsible for neurotoxicity. J Biol Chem. 2011;286(46):40151-62.
133. Becanovic K, Jagodic M, Sheng JR, Dahlman I, Aboul-Enein F, Wallstrom E, Olofsson P, Holmdahl R, Lassmann H, Olsson T. Advanced intercross line mapping of Eae5 reveals Ncf-1 and CLDN4 as candidate genes for experimental autoimmune encephalomyelitis. J Immunol. 2006;176:6055-64.
134. Hultqvist M, Olofsson P, Holmberg J, Backstrom BT, Tordsson J, Holmdahl R. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci U S A. 2004;101:12646-51.
135. van der Veen RC, Dietlin TA, Hofman FM, Pen L, Segal BH, Holland SM. Superoxide prevents nitric oxide-mediated suppression of helper T lymphocytes: decreased autoimmune encephalomyelitis in nicotinamide adenine dinucleotide phosphate oxidase knockout mice. J Immunol. 2000;164:5177-83.
136. Li S, Vana AC, Ribeiro R, Zhang Y. Distinct role of nitric oxide and peroxynitrite in mediating oligodendrocyte toxicity in culture and in experimental autoimmune encephalomyelitis. Neuroscience. 2011;184:107-19.
137. Qian L, Wei SJ, Zhang D, Hu X, Xu Z, Wilson B, El-Benna J, Hong JS, Flood PM. Potent anti-inflammatory and neuroprotective effects of TGF-beta1 are mediated through the inhibition of ERK and p47phox-Ser345 phosphorylation and translocation in microglia. J Immunol. 2008;181:660-8.
138. Qian L, Xu Z, Zhang W, Wilson B, Hong JS, Flood PM. Sinomenine, a natural dextrorotatory morphinan analog, is anti-inflammatory and neuroprotective through inhibition of microglial NADPH oxidase. J Neuroinflammation. 2007;4:23.
139. Yang S, Yang J, Yang Z, Chen P, Fraser A, Zhang W, Pang H, Gao X, Wilson B, Hong JS, Block ML. Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and PACAP4-6 are neuroprotective through inhibition of NADPH oxidase: potent regulators of microgliamediated oxidative stress. J Pharmacol Exp Ther. 2006;319:595-603.
140. Zhang D, Hu X, Wei SJ, Liu J, Gao H, Qian L, Wilson B, Liu G, Hong JS. Squamosamide derivative FLZ protects dopaminergic neurons against inflammation-mediated neurodegeneration through the inhibition of NADPH oxidase activity. J Neuroinflammation. 2008;5:21.
141. Zhang F, Shi JS, Zhou H, Wilson B, Hong JS, Gao HM. Resveratrol protects dopamine neurons against lipopolysaccharide-induced neurotoxicity through its anti-inflammatory actions. Mol Pharmacol. 2010;78:466-77.
142. Liu Y, Lo YC, Qian L, Crews FT, Wilson B, Chen HL, Wu HM, Chen SH, Wei K, Lu RB, Ali S, Hong JS. Verapamil protects dopaminergic neuron damage through a novel antiinflammatory mechanism by inhibition of microglial activation. Neuropharmacology. 2011;60:373-80.
143. Zhang F, Qian L, Flood PM, Shi JS, Hong JS, Gao HM. Inhibition of IkappaB kinase-beta protects dopamine neurons against lipopolysaccharide-induced neurotoxicity. J Pharmacol Exp Ther. 2010;333:822-33.
144. Choi SH, Lee DY, Chung ES, Hong YB, Kim SU, Jin BK. Inhibition of thrombin-induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo. J Neurochem. 2005;95:1755-65.
145. Zhang QG, Raz L, Wang R, Han D, De Sevilla L, Yang F, Vadlamudi RK, Brann DW. Estrogen attenuates ischemic oxidative damage via an estrogen receptor alpha-mediated inhibition of NADPH oxidase activation. J Neurosci. 2009;29:13823-36.
146. Egea J, Martin-de-Saavedra MD, Parada E, Romero A, Del Barrio L, Rosa AO, Garcia AG, Lopez MG. Galantamine elicits neuroprotection by inhibiting iNOS, NADPH oxidase and ROS in hippocampal slices stressed with anoxia/reoxygenation. Neuropharmacology. 2012; 62:1082-90.
147. Chechneva OV, Mayrhofer F, Daugherty DJ, Pleasure DE, Hong JS, Deng W. Low dose dextromethorphan attenuates moderate experimental autoimmune encephalomyelitis by inhibiting NOX2 and reducing peripheral immune cells infiltration in the spinal cord. Neurobiol Dis. 2011;44:63-72.
148. Drummond GR, Selemidis S, Griendling KK, Sobey CG. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov. 2011;10: 453-71.
149. Jaquet V, Scapozza L, Clark RA, Krause KH, Lambeth JD. Small-molecule NOX inhibitors: ROS-generating NADPH oxidases as therapeutic targets. Antioxid Redox Signal. 2009; 11:2535-52.