Oxidative stress in multiple sclerosis: Central and peripheral mode of action

Experimental Neurology

Volumn 277, Issue , 2016, Pages 58-67

  Ohl, Kim ^a   Tenbrock, Klaus ^a   Kipp, Markus ^b  

^a RWTH AACHEN UNIVERSITY   (Germany)

^b UNIVERSITY OF MUNICH   (Germany)

Author keywords

DMF; Neurodegeneration; Neuroprotection; Nrf2

Indexed keywords

BETA INTERFERON; CEFTRIAXONE; CHITOSAN; FINGOLIMOD; FUMARIC ACID DERIVATIVE; FUMARIC ACID DIMETHYL ESTER; FUMARIC ACID METHYL ESTER; KELCH LIKE ECH ASSOCIATED PROTEIN 1; REACTIVE OXYGEN METABOLITE; SULFORAPHANE; TRANSCRIPTION FACTOR NRF2;

ADAPTIVE IMMUNITY; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIOXIDANT RESPONSIVE ELEMENT; APOPTOSIS; AXONAL INJURY; DEMYELINATION; DISEASE COURSE; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG METABOLISM; DRUG TARGETING; EFFECTOR CELL; HUMAN; INFLAMMATION; LYMPHOCYTE PROLIFERATION; MACROPHAGE; MICROGLIA; MULTIPLE SCLEROSIS; NERVE DEGENERATION; NEUROPROTECTION; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION; NERVOUS SYSTEM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

HUMANS; MULTIPLE SCLEROSIS; NERVOUS SYSTEM; OXIDATIVE STRESS;

EID: 84951050495     PISSN: 00144886     EISSN: 10902430     Source Type: Journal    
DOI: 10.1016/j.expneurol.2015.11.010     Document Type: Review

References (125)

1. Altmeyer P.J., Matthes U., Pawlak F., Hoffmann K., Frosch P.J., Ruppert P., Wassilew S.W., Horn T., Kreysel H.W., Lutz G., et al. Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients. J. Am. Acad. Dermatol. 1994, 30:977-981.
2. Angelini G., Gardella S., Ardy M., Ciriolo M.R., Filomeni G., Di Trapani G., Clarke F., Sitia R., Rubartelli A. Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation. Proc. Natl. Acad. Sci. U. S. A. 2002, 99:1491-1496.
3. Barnett M.H., Prineas J.W. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann. Neurol. 2004, 55:458-468.
4. Bo L., Geurts J.J., Mork S.J., van der Valk P. Grey matter pathology in multiple sclerosis. Acta Neurol. Scand. Suppl. 2006, 183:48-50.
5. + regulatory T cells. Nat. Rev. Immunol. 2011, 11:119-130.
6. Carbone F., De Rosa V., Carrieri P.B., Montella S., Bruzzese D., Porcellini A., Procaccini C., La Cava A., Matarese G. Regulatory T cell proliferative potential is impaired in human autoimmune disease. Nat. Med. 2014, 20:69-74.
7. Cervellati C., Romani A., Fainardi E., Trentini A., Squerzanti M., Baldi E., Caniatti M.L., Granieri E., Bellini T., Castellazzi M. Serum ferroxidase activity in patients with multiple sclerosis: a pilot study. In Vivo 2014, 28:1197-1200.
8. Chen Y., Kuchroo V.K., Inobe J., Hafler D.A., Weiner H.L. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science (New York, N.Y.) 1994, 265:1237-1240.
9. Chen H., Assmann J.C., Krenz A., Rahman M., Grimm M., Karsten C.M., Kohl J., Offermanns S., Wettschureck N., Schwaninger M. Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate's protective effect in EAE. J. Clin. Invest. 2014, 124:2188-2192.
10. Colton C.A., Gilbert D.L. Microglia, an in vivo source of reactive oxygen species in the brain. Adv. Neurol. 1993, 59:321-326.
11. Compston A., Coles A. Multiple sclerosis. Lancet 2008, 372:1502-1517.
12. Cruz-Guilloty F., Saeed A.M., Duffort S., Cano M., Ebrahimi K.B., Ballmick A., Tan Y., Wang H., Laird J.M., Salomon R.G., Handa J.T., Perez V.L. T cells and macrophages responding to oxidative damage cooperate in pathogenesis of a mouse model of age-related macular degeneration. PLoS One 2014, 9.
13. Danilov C.A., Chandrasekaran K., Racz J., Soane L., Zielke C., Fiskum G. Sulforaphane protects astrocytes against oxidative stress and delayed death caused by oxygen and glucose deprivation. Glia 2009, 57:645-656.
14. de Jong R., Bezemer A.C., Zomerdijk T.P., van de Pouw-Kraan T., Ottenhoff T.H., Nibbering P.H. Selective stimulation of T helper 2 cytokine responses by the anti-psoriasis agent monomethylfumarate. Eur. J. Immunol. 1996, 26:2067-2074.
15. Dehmel T., Dobert M., Pankratz S., Leussink V.I., Hartung H.P., Wiendl H., Kieseier B.C. Monomethylfumarate reduces in vitro migration of mononuclear cells. Neurol. Sci. 2014, 35:1121-1125.
16. Devadas S., Zaritskaya L., Rhee S.G., Oberley L., Williams M.S. Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J. Exp. Med. 2002, 195:59-70.
17. + regulatory T cells in human autoimmune disease. Nat. Med. 2011, 17:673-675.
18. Ermis U., Weis J., Schulz J.B. PML in a patient treated with fumaric acid. N. Engl. J. Med. 2013, 368:1657-1658.
19. Esen N., Rainey-Barger E.K., Huber A.K., Blakely P.K., Irani D.N. Type-I interferons suppress microglial production of the lymphoid chemokine, CXCL13. Glia 2014, 62:1452-1462.
20. Favreau L.V., Pickett C.B. Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J. Biol. Chem. 1991, 266:4556-4561.
21. Fiorini A., Koudriavtseva T., Bucaj E., Coccia R., Foppoli C., Giorgi A., Schinina M.E., Di Domenico F., De Marco F., Perluigi M. Involvement of oxidative stress in occurrence of relapses in multiple sclerosis: the spectrum of oxidatively modified serum proteins detected by proteomics and redox proteomics analysis. PLoS One 2013, 8.
22. Fischer M.T., Sharma R., Lim J.L., Haider L., Frischer J.M., Drexhage J., Mahad D., Bradl M., van Horssen J., Lassmann H. NADPH oxidase expression in active multiple sclerosis lesions in relation to oxidative tissue damage and mitochondrial injury. Brain 2012, 135:886-899.
23. Fischer M.T., Wimmer I., Hoftberger R., Gerlach S., Haider L., Zrzavy T., Hametner S., Mahad D., Binder C.J., Krumbholz M., Bauer J., Bradl M., Lassmann H. Disease-specific molecular events in cortical multiple sclerosis lesions. Brain 2013, 136:1799-1815.
24. Fletcher J.M., Lalor S.J., Sweeney C.M., Tubridy N., Mills K.H. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. 2010, 162:1-11.
25. Fontenot J.D., Gavin M.A., Rudensky A.Y. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 2003, 4:330-336.
26. Forman H.J., Zhang H., Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol. Asp. Med. 2009, 30:1-12.
27. Forte M., Gold B.G., Marracci G., Chaudhary P., Basso E., Johnsen D., Yu X., Fowlkes J., Rahder M., Stem K., Bernardi P., Bourdette D. Cyclophilin D inactivation protects axons in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:7558-7563.
28. Friling R.S., Bensimon A., Tichauer Y., Daniel V. Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element. Proc. Natl. Acad. Sci. U. S. A. 1990, 87:6258-6262.
29. Frischer J.M., Weigand S.D., Guo Y., Kale N., Parisi J.E., Pirko I., Mandrekar J., Bramow S., Metz I., Bruck W., Lassmann H., Lucchinetti C.F. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann. Neurol. 2015.
30. Frisullo G., Nociti V., Iorio R., Patanella A.K., Caggiula M., Marti A., Sancricca C., Angelucci F., Mirabella M., Tonali P.A., Batocchi A.P. Regulatory T cells fail to suppress CD4T+-bet+ T cells in relapsing multiple sclerosis patients. Immunology 2009, 127:418-428.
31. Gabrilovich D.I., Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 2009, 9:162-174.
32. Gartner D., Hoff H., Gimsa U., Burmester G.R., Brunner-Weinzierl M.C. CD25 regulatory T cells determine secondary but not primary remission in EAE: impact on long-term disease progression. J. Neuroimmunol. 2006, 172:73-84.
33. Gelderman K.A., Hultqvist M., Holmberg J., Olofsson P., Holmdahl R. T cell surface redox levels determine T cell reactivity and arthritis susceptibility. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:12831-12836.
34. Gergely P., Niland B., Gonchoroff N., Pullmann R., Phillips P.E., Perl A. Persistent mitochondrial hyperpolarization, increased reactive oxygen intermediate production, and cytoplasmic alkalinization characterize altered IL-10 signaling in patients with systemic lupus erythematosus. J. Immunol. 2002, 169:1092-1101.
35. Ghoreschi K., Bruck J., Kellerer C., Deng C., Peng H., Rothfuss O., Hussain R.Z., Gocke A.R., Respa A., Glocova I., Valtcheva N., Alexander E., Feil S., Feil R., Schulze-Osthoff K., Rupec R.A., Lovett-Racke A.E., Dringen R., Racke M.K., Rocken M. Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. J. Exp. Med. 2011, 208:2291-2303.
36. Gironi M., Borgiani B., Mariani E., Cursano C., Mendozzi L., Cavarretta R., Saresella M., Clerici M., Comi G., Rovaris M., Furlan R. Oxidative stress is differentially present in multiple sclerosis courses, early evident, and unrelated to treatment. J. Immunol. Res. 2014, 2014:961863.
37. Gray E., Thomas T.L., Betmouni S., Scolding N., Love S. Elevated activity and microglial expression of myeloperoxidase in demyelinated cerebral cortex in multiple sclerosis. Brain Pathol. 2008, 18:86-95.
38. Gray E., Thomas T.L., Betmouni S., Scolding N., Love S. Elevated myeloperoxidase activity in white matter in multiple sclerosis. Neurosci. Lett. 2008, 444:195-198.
39. Guan J.Z., Guan W.P., Maeda T., Guoqing X., GuangZhi W., Makino N. Patients with multiple sclerosis show increased oxidative stress markers and somatic telomere length shortening. Mol. Cell. Biochem. 2015, 400:183-187.
40. Gutscher M., Pauleau A.L., Marty L., Brach T., Wabnitz G.H., Samstag Y., Meyer A.J., Dick T.P. Real-time imaging of the intracellular glutathione redox potential. Nat. Methods 2008, 5:553-559.
41. Haas J., Hug A., Viehover A., Fritzsching B., Falk C.S., Filser A., Vetter T., Milkova L., Korporal M., Fritz B., Storch-Hagenlocher B., Krammer P.H., Suri-Payer E., Wildemann B. Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cell immune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis. Eur. J. Immunol. 2005, 35:3343-3352.
42. Haider L., Fischer M.T., Frischer J.M., Bauer J., Hoftberger R., Botond G., Esterbauer H., Binder C.J., Witztum J.L., Lassmann H. Oxidative damage in multiple sclerosis lesions. Brain 2011, 134:1914-1924.
43. Hermans G., Stinissen P., Hauben L., Van den Berg-Loonen E., Raus J., Zhang J. Cytokine profile of myelin basic protein-reactive T cells in multiple sclerosis and healthy individuals. Ann. Neurol. 1997, 42:18-27.
44. Hildeman D.A., Mitchell T., Teague T.K., Henson P., Day B.J., Kappler J., Marrack P.C. Reactive oxygen species regulate activation-induced T cell apoptosis. Immunity 1999, 10:735-744.
45. Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science (New York, N.Y.) 2003, 299:1057-1061.
46. Huan J., Culbertson N., Spencer L., Bartholomew R., Burrows G.G., Chou Y.K., Bourdette D., Ziegler S.F., Offner H., Vandenbark A.A. Decreased FOXP3 levels in multiple sclerosis patients. J. Neurosci. Res. 2005, 81:45-52.
47. Im K.I., Kim N., Lim J.Y., Nam Y.S., Lee E.S., Kim E.J., Kim H.J., Kim S.H., Cho S.G. The free radical scavenger NecroX-7 attenuates acute graft-versus-host disease via reciprocal regulation of Th1/regulatory T cells and inhibition of HMGB1 release. J. Immunol. 2015.
48. Imaizumi S., Kondo T., Deli M.A., Gobbel G., Joo F., Epstein C.J., Yoshimoto T., Chan P.H. The influence of oxygen free radicals on the permeability of the monolayer of cultured brain endothelial cells. Neurochem. Int. 1996, 29:205-211.
49. Innamorato N.G., Rojo A.I., Garcia-Yague A.J., Yamamoto M., de Ceballos M.L., Cuadrado A. The transcription factor Nrf2 is a therapeutic target against brain inflammation. J. Immunol. 2008, 181:680-689.
50. Johnson D.A., Amirahmadi S., Ward C., Fabry Z., Johnson J.A. The absence of the pro-antioxidant transcription factor Nrf2 exacerbates experimental autoimmune encephalomyelitis. Toxicol. Sci. 2010, 114:237-246.
51. Kaminski M.M., Roth D., Krammer P.H., Gulow K. Mitochondria as oxidative signaling organelles in T-cell activation: physiological role and pathological implications. Arch. Immunol. Ther. Exp. 2013, 61:367-384.
52. Karlik M., Valkovic P., Hancinova V., Krizova L., Tothova L., Celec P. Markers of oxidative stress in plasma and saliva in patients with multiple sclerosis. Clin. Biochem. 2015, 48:24-28.
53. Kensler T.W., Wakabayashi N., Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol. 2007, 47:89-116.
54. Kesarwani P., Murali A.K., Al-Khami A.A., Mehrotra S. Redox regulation of T-cell function: from molecular mechanisms to significance in human health and disease. Antioxid. Redox Signal. 2013, 18:1497-1534.
55. Khodagholi F., Eftekharzadeh B., Maghsoudi N., Rezaei P.F. Chitosan prevents oxidative stress-induced amyloid beta formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-kappaB. Mol. Cell. Biochem. 2010, 337:39-51.
56. Khor T.O., Huang M.T., Kwon K.H., Chan J.Y., Reddy B.S., Kong A.N. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Res. 2006, 66:11580-11584.
57. Kipp M., Amor S. FTY720 on the way from the base camp to the summit of the mountain: relevance for remyelination. Mult. Scler. 2012, 18:258-263.
58. Koch M., Mostert J., Arutjunyan A., Stepanov M., Teelken A., Heersema D., De Keyser J. Peripheral blood leukocyte NO production and oxidative stress in multiple sclerosis. Mult. Scler. 2008, 14:159-165.
59. Kohm A.P., Carpentier P.A., Anger H.A., Miller S.D. Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol. 2002, 169:4712-4716.
60. Korn T., Reddy J., Gao W., Bettelli E., Awasthi A., Petersen T.R., Backstrom B.T., Sobel R.A., Wucherpfennig K.W., Strom T.B., Oukka M., Kuchroo V.K. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat. Med. 2007, 13:423-431.
61. Kraaij M.D., Savage N.D., van der Kooij S.W., Koekkoek K., Wang J., van den Berg J.M., Ottenhoff T.H., Kuijpers T.W., Holmdahl R., van Kooten C., Gelderman K.A. Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:17686-17691.
62. Lewerenz J., Albrecht P., Tien M.L., Henke N., Karumbayaram S., Kornblum H.I., Wiedau-Pazos M., Schubert D., Maher P., Methner A. Induction of Nrf2 and xCT are involved in the action of the neuroprotective antibiotic ceftriaxone in vitro. J. Neurochem. 2009, 111:332-343.
63. Lin M.T., Beal M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 2006, 443:787-795.
64. Lin S.X., Lisi L., Dello Russo C., Polak P.E., Sharp A., Weinberg G., Kalinin S., Feinstein D.L. The anti-inflammatory effects of dimethyl fumarate in astrocytes involve glutathione and haem oxygenase-1. ASN Neuro 2011, 3.
65. Linker R.A., Lee D.H., Ryan S., van Dam A.M., Conrad R., Bista P., Zeng W., Hronowsky X., Buko A., Chollate S., Ellrichmann G., Bruck W., Dawson K., Goelz S., Wiese S., Scannevin R.H., Lukashev M., Gold R. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 2011, 134:678-692.
66. Litjens N.H., Rademaker M., Ravensbergen B., Rea D., van der Plas M.J., Thio B., Walding A., van Dissel J.T., Nibbering P.H. Monomethylfumarate affects polarization of monocyte-derived dendritic cells resulting in down-regulated Th1 lymphocyte responses. Eur. J. Immunol. 2004, 34:565-575.
67. Lock C., Hermans G., Pedotti R., Brendolan A., Schadt E., Garren H., Langer-Gould A., Strober S., Cannella B., Allard J., Klonowski P., Austin A., Lad N., Kaminski N., Galli S.J., Oksenberg J.R., Raine C.S., Heller R., Steinman L. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 2002, 8:500-508.
68. Los M., Schenk H., Hexel K., Baeuerle P.A., Droge W., Schulze-Osthoff K. IL-2 gene expression and NF-kappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase. EMBO J. 1995, 14:3731-3740.
69. Lowther D.E., Chong D.L., Ascough S., Ettorre A., Ingram R.J., Boyton R.J., Altmann D.M. Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response. Acta Neuropathol. 2013, 126:501-515.
70. Lucas M., Rodriguez M.C., Gata J.M., Zayas M.D., Solano F., Izquierdo G. Regulation by interferon beta-1a of reactive oxygen metabolites production by lymphocytes and monocytes and serum sulfhydryls in relapsing multiple sclerosis patients. Neurochem. Int. 2003, 42:67-71.
71. Lucchinetti C., Bruck W., Parisi J., Scheithauer B., Rodriguez M., Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 2000, 47:707-717.
72. Ma Q., Battelli L., Hubbs A.F. Multiorgan autoimmune inflammation, enhanced lymphoproliferation, and impaired homeostasis of reactive oxygen species in mice lacking the antioxidant-activated transcription factor Nrf2. Am. J. Pathol. 2006, 168:1960-1974.
73. Matsue H., Edelbaum D., Shalhevet D., Mizumoto N., Yang C., Mummert M.E., Oeda J., Masayasu H., Takashima A. Generation and function of reactive oxygen species in dendritic cells during antigen presentation. J. Immunol. 2003, 171:3010-3018.
74. McGeachy M.J., Stephens L.A., Anderton S.M. Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. J. Immunol. 2005, 175:3025-3032.
75. Moline-Velazquez V., Cuervo H., Vila-Del Sol V., Ortega M.C., Clemente D., de Castro F. Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis. Brain Pathol. 2011, 21:678-691.
76. Mougiakakos D., Johansson C.C., Kiessling R. Naturally occurring regulatory T cells show reduced sensitivity toward oxidative stress-induced cell death. Blood 2009, 113:3542-3545.
77. Nguyen T., Nioi P., Pickett C.B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 2009, 284:13291-13295.
78. Nieuwkamp D.J., Murk J.L., van Oosten B.W., Cremers C.H., Killestein J., Viveen M.C., Van Hecke W., Frijlink D.W., Wattjes M.P. PML in a patient without severe lymphocytopenia receiving dimethyl fumarate. N. Engl. J. Med. 2015, 372:1474-1476.
79. O'Connor R.A., Malpass K.H., Anderton S.M. The inflamed central nervous system drives the activation and rapid proliferation of Foxp3+ regulatory T cells. J. Immunol. 2007, 179:958-966.
80. Olesen S.P. Free oxygen radicals decrease electrical resistance of microvascular endothelium in brain. Acta Physiol. Scand. 1987, 129:181-187.
81. Osburn W.O., Yates M.S., Dolan P.D., Chen S., Liby K.T., Sporn M.B., Taguchi K., Yamamoto M., Kensler T.W. Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice. Toxicol. Sci. 2008, 104:218-227.
82. Pae H.O., Oh G.S., Choi B.M., Chae S.C., Chung H.T. Differential expressions of heme oxygenase-1 gene in CD25- and CD25+ subsets of human CD4+ T cells. Biochem. Biophys. Res. Commun. 2003, 306:701-705.
83. Pani G., Colavitti R., Borrello S., Galeotti T. Redox regulation of lymphocyte signaling. IUBMB Life 2000, 49:381-389.
84. Pasquali L., Pecori C., Lucchesi C., LoGerfo A., Iudice A., Siciliano G., Bonuccelli U. Plasmatic oxidative stress biomarkers in multiple sclerosis: relation with clinical and demographic characteristics. Clin. Biochem. 2015, 48:19-23.
85. Peng H., Guerau-de-Arellano M., Mehta V.B., Yang Y., Huss D.J., Papenfuss T.L., Lovett-Racke A.E., Racke M.K. Dimethyl fumarate inhibits dendritic cell maturation via nuclear factor kappaB (NF-kappaB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) and mitogen stress-activated kinase 1 (MSK1) signaling. J. Biol. Chem. 2012, 287:28017-28026.
86. Qi X., Lewin A.S., Sun L., Hauswirth W.W., Guy J. Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis. Invest. Ophthalmol. Vis. Sci. 2007, 48:681-691.
87. Rajah T., Chow S.C. The inhibition of human T cell proliferation by the caspase inhibitor z-VAD-FMK is mediated through oxidative stress. Toxicol. Appl. Pharmacol. 2014, 278:100-106.
88. Ramsey C.P., Glass C.A., Montgomery M.B., Lindl K.A., Ritson G.P., Chia L.A., Hamilton R.L., Chu C.T., Jordan-Sciutto K.L. Expression of Nrf2 in neurodegenerative diseases. J. Neuropathol. Exp. Neurol. 2007, 66:75-85.
89. Rangasamy T., Guo J., Mitzner W.A., Roman J., Singh A., Fryer A.D., Yamamoto M., Kensler T.W., Tuder R.M., Georas S.N., Biswal S. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. J. Exp. Med. 2005, 202:47-59.
90. Reddy N.M., Kleeberger S.R., Kensler T.W., Yamamoto M., Hassoun P.M., Reddy S.P. Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice. J. Immunol. 2009, 182:7264-7271.
91. Reth M. Hydrogen peroxide as second messenger in lymphocyte activation. Nat. Immunol. 2002, 3:1129-1134.
92. Rockwell C.E., Zhang M., Fields P.E., Klaassen C.D. Th2 skewing by activation of Nrf2 in CD4(+) T cells. J. Immunol. 2012, 188:1630-1637.
93. Rosenkranz T., Novas M., Terborg C. PML in a patient with lymphocytopenia treated with dimethyl fumarate. N. Engl. J. Med. 2015, 372:1476-1478.
94. Rubant S.A., Ludwig R.J., Diehl S., Hardt K., Kaufmann R., Pfeilschifter J.M., Boehncke W.H. Dimethylfumarate reduces leukocyte rolling in vivo through modulation of adhesion molecule expression. J. Invest. Dermatol. 2008, 128:326-331.
95. Ruuls S.R., Bauer J., Sontrop K., Huitinga I., t Hart B.A., Dijkstra C.D. Reactive oxygen species are involved in the pathogenesis of experimental allergic encephalomyelitis in Lewis rats. J. Neuroimmunol. 1995, 56:207-217.
96. Sarlette A., Krampfl K., Grothe C., Neuhoff N., Dengler R., Petri S. Nuclear erythroid 2-related factor 2-antioxidative response element signaling pathway in motor cortex and spinal cord in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 2008, 67:1055-1062.
97. Schachtele S.J., Hu S., Lokensgard J.R. Modulation of experimental herpes encephalitis-associated neurotoxicity through sulforaphane treatment. PLoS One 2012, 7.
98. Schluesener H.J., Seid K. Heme oxygenase-1 in lesions of rat experimental autoimmune encephalomyelitis and neuritis. J. Neuroimmunol. 2000, 110:114-120.
99. Schuh C., Wimmer I., Hametner S., Haider L., Van Dam A.M., Liblau R.S., Smith K.J., Probert L., Binder C.J., Bauer J., Bradl M., Mahad D., Lassmann H. Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models. Acta Neuropathol. 2014, 128:247-266.
100. Secchi C., Carta M., Crescio C., Spano A., Arras M., Caocci G., Galimi F., La Nasa G., Pippia P., Turrini F., Pantaleo A. T cell tyrosine phosphorylation response to transient redox stress. Cell. Signal. 2015, 27:777-788.
101. Sekizawa T., Sasaki M., Kumagai K., Takase S., Nakamura S. B lymphocytes bearing immunoglobulins in multiple sclerosis. Tohoku J. Exp. Med. 1974, 114:395-397.
102. Sian J., Dexter D.T., Lees A.J., Daniel S., Agid Y., Javoy-Agid F., Jenner P., Marsden C.D. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann. Neurol. 1994, 36:348-355.
103. Slowik A., Schmidt T., Beyer C., Amor S., Clarner T., Kipp M. The sphingosine 1-phosphate receptor agonist FTY720 is neuroprotective after cuprizone-induced CNS demyelination. Br. J. Pharmacol. 2015, 172:80-92.
104. Stys P.K., Zamponi G.W., van Minnen J., Geurts J.J. Will the real multiple sclerosis please stand up? Nature reviews. Neuroscience 2012, 13:507-514.
105. Suthanthiran M., Anderson M.E., Sharma V.K., Meister A. Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc. Natl. Acad. Sci. U. S. A. 1990, 87:3343-3347.
106. Tadokoro C.E., Shakhar G., Shen S., Ding Y., Lino A.C., Maraver A., Lafaille J.J., Dustin M.L. Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo. J. Exp. Med. 2006, 203:505-511.
107. Thimmulappa R.K., Scollick C., Traore K., Yates M., Trush M.A., Liby K.T., Sporn M.B., Yamamoto M., Kensler T.W., Biswal S. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem. Biophys. Res. Commun. 2006, 351:883-889.
108. Trapp B.D., Nave K.A. Multiple sclerosis: an immune or neurodegenerative disorder?. Annu. Rev. Neurosci. 2008, 31:247-269.
109. Treumer F., Zhu K., Glaser R., Mrowietz U. Dimethylfumarate is a potent inducer of apoptosis in human T cells. J. Invest. Dermatol. 2003, 121:1383-1388.
110. Tripathi P., Hildeman D. Sensitization of T cells to apoptosis-a role for ROS?. Apoptosis 2004, 9:515-523.
111. Tse H.M., Milton M.J., Schreiner S., Profozich J.L., Trucco M., Piganelli J.D. Disruption of innate-mediated proinflammatory cytokine and reactive oxygen species third signal leads to antigen-specific hyporesponsiveness. J. Immunol. 2007, 178:908-917.
112. Tzartos J.S., Friese M.A., Craner M.J., Palace J., Newcombe J., Esiri M.M., Fugger L. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am. J. Pathol. 2008, 172:146-155.
113. van der Goes A., Brouwer J., Hoekstra K., Roos D., van den Berg T.K., Dijkstra C.D. Reactive oxygen species are required for the phagocytosis of myelin by macrophages. J. Neuroimmunol. 1998, 92:67-75.
114. van der Star B.J., Vogel D.Y., Kipp M., Puentes F., Baker D., Amor S. In vitro and in vivo models of multiple sclerosis. CNS Neurol. Disord. Drug Targets 2012, 11:570-588.
115. Venken K., Hellings N., Broekmans T., Hensen K., Rummens J.L., Stinissen P. Natural naive CD4+CD25+CD127low regulatory T cell (Treg) development and function are disturbed in multiple sclerosis patients: recovery of memory Treg homeostasis during disease progression. J. Immunol. 2008, 180:6411-6420.
116. Vergara D., Martignago R., Bonsegna S., De Nuccio F., Santino A., Nicolardi G., Maffia M. IFN-beta reverses the lipopolysaccharide-induced proteome modifications in treated astrocytes. J. Neuroimmunol. 2010, 221:115-120.
117. Viglietta V., Baecher-Allan C., Weiner H.L., Hafler D.A. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 2004, 199:971-979.
118. Wang P., Xie K., Wang C., Bi J. Oxidative stress induced by lipid peroxidation is related with inflammation of demyelination and neurodegeneration in multiple sclerosis. Eur. Neurol. 2014, 72:249-254.
119. Wilms H., Sievers J., Rickert U., Rostami-Yazdi M., Mrowietz U., Lucius R. Dimethylfumarate inhibits microglial and astrocytic inflammation by suppressing the synthesis of nitric oxide, IL-1beta, TNF-alpha and IL-6 in an in-vitro model of brain inflammation. J. Neuroinflammation 2010, 7:30.
120. Yan Z., Garg S.K., Kipnis J., Banerjee R. Extracellular redox modulation by regulatory T cells. Nat. Chem. Biol. 2009, 5:721-723.
121. Yan Z., Garg S.K., Banerjee R. Regulatory T cells interfere with glutathione metabolism in dendritic cells and T cells. J. Biol. Chem. 2010, 285:41525-41532.
122. Yi H., Guo C., Yu X., Zuo D., Wang X.Y. Mouse CD11b+Gr-1+ myeloid cells can promote Th17 cell differentiation and experimental autoimmune encephalomyelitis. J. Immunol. 2012, 189:4295-4304.
123. Zhang D.D., Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol. Cell. Biol. 2003, 23:8137-8151.
124. Zhang Q., Fujino M., Xu J., Li X.K. The role and potential therapeutic application of myeloid-derived suppressor cells in allo- and autoimmunity. Mediat. Inflamm. 2015, 2015:421927.
125. Zhu J., Paul W.E. Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol. Rev. 2010, 238:247-262.