Novel targets in multiple sclerosis: To oxidative stress and beyond

Current Topics in Medicinal Chemistry

Volumn 14, Issue 22, 2014, Pages 2590-2599

  Chiurchiù, Valerio ^a  

^a IRCCS FONDAZIONE SANTA LUCIA   (Italy)

Author keywords

Inflammation; Multiple sclerosis; Neurodegeneration; Oxidative stress; Remyelination; Therapeutics

Indexed keywords

ALEMTUZUMAB; AMILORIDE; ATORVASTATIN; BETA1A INTERFERON; DACLIZUMAB; FINGOLIMOD; FUMARIC ACID DIMETHYL ESTER; GLATIRAMER; INTERFERON BETA SERINE; INTERLEUKIN 10; INTERLEUKIN 4; LAQUINIMOD; MATRIX METALLOPROTEINASE; METHYLPREDNISOLONE; MINOCYCLINE; MITOXANTRONE; NABIXIMOLS; NATALIZUMAB; OCRELIZUMAB; OFATUMUMAB; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; RITUXIMAB; SPHINGOSINE 1 PHOSPHATE RECEPTOR; SUPEROXIDE DISMUTASE; TERIFLUNOMIDE; TRANSCRIPTION FACTOR NRF2; TRANSFORMING GROWTH FACTOR BETA; UNINDEXED DRUG; VERY LATE ACTIVATION ANTIGEN;

ARTICLE; BACKACHE; BLOOD BRAIN BARRIER; BRADYCARDIA; CARDIOTOXICITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL HETEROGENEITY; CHEMICAL STRUCTURE; CLINICAL TRIAL (TOPIC); DEPRESSION; DIARRHEA; DIZZINESS; DNA REPAIR; DRUG MECHANISM; DRUG TARGETING; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HAIR LOSS; HEADACHE; HUMAN; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOSUPPRESSIVE TREATMENT; INFECTION; INFLAMMATION; INFLUENZA; LIVER DYSFUNCTION; MULTIPLE SCLEROSIS; MYCOSIS; MYELIN SHEATH; NAUSEA; NERVE DEGENERATION; NEUROPROTECTION; OLIGODENDROCYTE PRECURSOR CELL; OXIDATIVE STRESS; PATHOGENESIS; RELAPSE; REMYELINIZATION; SWELLING; TH1 CELL; TH17 CELL; DRUG EFFECTS; IMMUNOLOGY; METABOLISM;

HUMANS; MULTIPLE SCLEROSIS; OXIDATIVE STRESS;

EID: 84921862397     PISSN: 15680266     EISSN: 18734294     Source Type: Journal    
DOI: 10.2174/1568026614666141203143801     Document Type: Article

References (77)

1. Noseworthy, J.H.; Lucchinetti, C.; Rodriguez, M.; Weinshenker, B.G. Multiple sclerosis. N. Engl. J. Med., 2000, 343(13), 938-52.
2. Compston, A.; Coles, A. Multiple sclerosis. Lancet, 2008, 372(9648), 1502-17.
3. McDonald, W.I.; Compston, A.; Edan, G.; Goodkin, D.; Hartung, H.P.; Lublin, F.D.; McFarland, H. F.; Paty, D. W.; Polman, C. H.; Reingold, S. C.; Sandberg-Wollheim, M.; Sibley, W.; Thompson, A.; van den Noort, S.; Weinshenker, B. Y.; Wolinsky, J. S. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann. Neurol., 2001, 50(1), 121-7.
4. Hafler, D.A.; Compston, A.; Sawcer, S.; Lander, E. S.; Daly, M. J.; De Jager, P.L.; de Bakker, P. I.; Gabriel, S. B.; Mirel, D. B.; Ivinson, A. J.; Pericak-Vance, M.A.; Gregory, S.G.; Rioux, J.D.; McCauley, J.L.; Haines, J.L.; Barcellos, L. F.; Cree, B.; Oksenberg, J. R.; Hauser, S. L. International Multiple Sclerosis Genetics Consortium. Risk alleles for multiple sclerosis identified by a genomewide study. N. Engl. J. Med., 2007, 357(9), 851-62.
5. Huynh, J.L.; Casaccia, P. Epigenetic mechanisms in multiple sclerosis: implications for pathogenesis and treatment. Lancet Neurol., 2013, 12(2), 195-206.
6. Broux, B.; Stinissen, P.; Hellings, N. Which immune cells matter? The immunopathogenesis of multiple sclerosis. Crit. Rev. Immunol., 2013, 33(4), 283-306.
7. Gandhi, R.; Laroni, A.; Weiner, H. L. Role of the innate immune system in the pathogenesis of multiple sclerosis. J. Neuroimmunol., 2010, 221(1-2), 7-14.
8. Trapp, B.D.; Nave, K.A. Multiple sclerosis: an immune or neurodegenerative disorder? Annu. Rev. Neurosci., 2008, (31), 247-69.
9. Lassmann, H.; van Horssen, J.; Mahad, D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol., 2012, 8(11), 647-56.
10. Weissert, R. The immune pathogenesis of multiple sclerosis. J. Neuroimmune. Pharmacol., 2013, 8 (4), 857-66.
11. Jadidi-Niaragh, F.; Mirshafiey, A. Th17 cell, the new player of neuroinflammatory process in multiple sclerosis. Scand. J. Immunol., 2011, 74(1), 1-13.
12. Buc, M. Role of regulatory T cells in pathogenesis and biological therapy of multiple sclerosis. Mediators Inflamm., 2013, 2013, 963748.
13. Denic, A.; Wootla, B.; Rodriguez, M. CD8(+) T cells in multiple sclerosis. Exp. Opin. Ther. Targets, 2013, 17(9), 1053-66.
14. Krumbholz, M.; Derfuss, T.; Hohlfeld, R.; Meinl, E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat. Rev. Neurol., 2012, 8(11), 613-23.
15. Karni, A.; Abraham, M.; Monsonego, A.; Cai, G.; Freeman, G.J.; Hafler, D.; Khoury, S. J.; Weiner, H. L. Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response. J. Immunol., 2006, 177(6), 4196-202.
16. Chiurchiu, V.; Cencioni, M.T.; Bisicchia, E.; De Bardi, M.; Gasperini, C.; Borsellino, G.; Centonze, D.; Battistini, L.; Maccarrone, M. Distinct modulation of human myeloid and plasmacytoid dendritic cells by anandamide in multiple sclerosis. Ann. Neurol., 2013, 73(5), 626-36.
17. Stasiolek, M.; Bayas, A.; Kruse, N.; Wieczarkowiecz, A.; Toyka, K. V.; Gold, R.; Selmaj, K. Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis. Brain, 2006, 129(Pt 5), 1293-305.
18. Haghikia, A.; Hohlfeld, R.; Gold, R.; Fugger, L. Therapies for multiple sclerosis: translational achievements and outstanding needs. Trends. Mol. Med., 2013, 19(5), 309-19.
19. Mahurkar, S.; Suppiah, V.; O'Doherty, C. Pharmacogenomics of interferon beta and glatiramer acetate response: a review of the literature. Autoimmun. Rev., 2014, 13(2), 178-86.
20. Gawronski, K.M.; Rainka, M.M.; Patel, M.J.; Gengo, F.M. Treatment options for multiple sclerosis: current and emerging therapies. Pharmacotherapy, 2010, 30(9), 916-27.
21. Menge, T.; Weber, M.S.; Hemmer, B.; Kieseier, B.C.; von Budingen, H.C.; Warnke, C.; Zamvil, S. S.; Boster, A.; Khan, O.; Hartung, H. P.; Stuve, O. Disease-modifying agents for multiple sclerosis: recent advances and future prospects. Drugs, 2008, 68(17), 2445-68.
22. Kantarci, O. H.; Pirko, I.; Rodriguez, M. Novel immunomodulatory approaches for the management of multiple sclerosis. Clin. Pharmacol. Ther., 2014, 95(1), 32-44.
23. O'Connor, P.; Wolinsky, J.S.; Confavreux, C.; Comi, G.; Kappos, L.; Olsson, T. P.; Benzerdjeb, H.; Truffinet, P.; Wang, L.; Miller, A.; Freedman, M. S.; Group, T. T. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N. Engl. J. Med., 2011, 365(14), 1293-303.
24. Confavreux, C.; O'Connor, P.; Comi, G.; Freedman, M.S.; Miller, A.E.; Olsson, T.P.; Wolinsky, J.S.; Bagulho, T.; Delhay, J.L.; Dukovic, D.; Truffinet, P.; Kappos, L.; TOWER Trial Group. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol., 2014, 13(3), 247-56.
25. Rommer, P.S.; Dudesek, A.; Stuve, O.; Zettl, U. K. Monoclonal antibodies in treatment of multiple sclerosis. Clin. Exp. Immunol., 2014, 175(3), 373-84.
26. Wingerchuk, D.M.; Carter, J.L. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin. Proc., 2014, 89(2), 225-40.
27. Comi, G.; Jeffery, D.; Kappos, L.; Montalban, X.; Boyko, A.; Rocca, M. A.; Filippi, M.; Group, A. S. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N. Engl. J. Med., 2012, 366(11), 1000-9.
28. Vollmer, T.L.; Sorensen, P.S.; Selmaj, K.; Zipp, F.; Havrdova, E.; Cohen, J. A.; Sasson, N.; Gilgun-Sherki, Y.; Arnold, D. L.; Group, B. S. A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. J. Neurol., 2014, 261(4), 773-83.
29. Haggiag, S.; Ruggieri, S.; Gasperini, C. Efficacy and safety of laquinimod in multiple sclerosis: current status. Ther Adv Neurol Disord., 2013, 6(6), 343-52.
30. Dhib-Jalbut, S. Pathogenesis of myelin/oligodendrocyte damage in multiple sclerosis. Neurology, 2007, 68(22 Suppl 3), S13-21; discussion S43-54.
31. Peferoen, L.; Kipp, M.; van der Valk, P.; van Noort, J. M.; Amor, S. Oligodendrocyte-microglia cross-talk in the central nervous system. Immunology, 2014, 141(3), 302-13.
32. Franklin, R.J.; ffrench-Constant, C.; Edgar, J. M.; Smith, K. J. Neuroprotection and repair in multiple sclerosis. Nature reviews. Neurology, 2012, 8(11), 624-34.
33. Cambron, M.; D'Haeseleer, M.; Laureys, G.; Clinckers, R.; Debruyne, J.; De Keyser, J. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis. J. Cereb. Blood Flow Metab., 2012, 32(3), 413-24.
34. Reynolds, R.; Roncaroli, F.; Nicholas, R.; Radotra, B.; Gveric, D.; Howell, O. The neuropathological basis of clinical progression in multiple sclerosis. Acta. Neuropathol., 2011, 122(2), 155-70.
35. Hartley, M.D.; Altowaijri, G.; Bourdette, D. Remyelination and multiple sclerosis: therapeutic approaches and challenges. Curr Neurol Neurosci Rep., 2014, 14(10), 485.
36. Chen, X.; Ma, X.; Jiang, Y.; Pi, R.; Liu, Y.; Ma, L. The prospects of minocycline in multiple sclerosis. J. Neuroimmunol., 2011, 235(1-2), 1-8.
37. Tanaka, T.; Murakami, K.; Bando, Y.; Yoshida, S. Minocycline reduces remyelination by suppressing ciliary neurotrophic factor expression after cuprizone-induced demyelination. J. Neurochem., 2013, 127(2), 259-70.
38. Gold, B.G.; Voda, J.; Yu, X.; McKeon, G.; Bourdette, D. N. FK506 and a nonimmunosuppressant derivative reduce axonal and myelin damage in experimental autoimmune encephalomyelitis: neuroimmunophilin ligand-mediated neuroprotection in a model of multiple sclerosis. J. Neurosci. Res., 2004, 77(3), 367-77.
39. Kamm, C.P.; El-Koussy, M.; Humpert, S.; Findling, O.; Burren, Y.; Schwegler, G.; Donati, F.; Muller, M.; Muller, F.; Slotboom, J.; Kappos, L.; Naegelin, Y.; Mattle, H. P.; Group, S. S. Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial. PloS One, 2014, 9(1), e86663.
40. Arun, T.; Tomassini, V.; Sbardella, E.; de Ruiter, M.B.; Matthews, L.; Leite, M. I.; Gelineau-Morel, R.; Cavey, A.; Vergo, S.; Craner, M.; Fugger, L.; Rovira, A.; Jenkinson, M.; Palace, J. Targeting ASIC1 in primary progressive multiple sclerosis: evidence of neuroprotection with amiloride. Brain, 2013, 136(Pt 1), 106-15.
41. Galve-Roperh, I.; Chiurchiu, V.; Diaz-Alonso, J.; Bari, M.; Guzman, M.; Maccarrone, M. Cannabinoid receptor signaling in progenitor/ stem cell proliferation and differentiation. Prog. Lipid Res., 2013, 52(4), 633-50.
42. Sanchez, A.J.; Garcia-Merino, A. Neuroprotective agents: cannabinoids. Clin. Immunol., 2012, 142(1), 57-67.
43. Stuve, O.; Paul, F. Progressive multiple sclerosis: desperately seeking remedy. Lancet Neurol., 2013, 12(9), 840-1.
44. Syed, Y. Y.; McKeage, K.; Scott, L.J. Delta-9- tetrahydrocannabinol/cannabidiol (Sativex®): a review of its use in patients with moderate to severe spasticity due to multiple sclerosis. Drugs, 2014, 74(5), 563-78.
45. Hauser, S. L.; Chan, J. R.; Oksenberg, J.R. Multiple sclerosis: Prospects and promise. Ann. Neurol., 2013, 74(3), 317-27.
46. Rodgers, J.M.; Robinson, A.P.; Miller, S.D. Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis. Discov. Med., 2013, 16(86), 53-63.
47. Chiurchiu, V.; Maccarrone, M.; Orlacchio, A. The role of reticulons in neurodegenerative diseases. Neuromolecular Med., 2014, 16(1), 3-15.
48. Lee, J.Y.; Petratos, S. Multiple sclerosis: does Nogo play a role? Neuroscientist, 2013, 19(4), 394-408.
49. Satoh, J.; Onoue, H.; Arima, K.; Yamamura, T. Nogo-A and nogo receptor expression in demyelinating lesions of multiple sclerosis. J Neuropathol Exp Neurol., 2005, 64(2), 129-38.
50. Mi, S.; Hu, B.; Hahm, K.; Luo, Y.; Kam Hui, E. S.; Yuan, Q.; Wong, W. M.; Wang, L.; Su, H.; Chu, T. H.; Guo, J.; Zhang, W.; So, K. F.; Pepinsky, B.; Shao, Z.; Graff, C.; Garber, E.; Jung, V.; Wu, E. X.; Wu, W. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. Nat. Med., 2007, 13(10), 1228-33.
51. Mi S, Pepinsky RB, Cadavid D. Blocking LINGO-1 as a therapy to promote CNS repair: from concept to the clinic. CNS Drugs, 2013, 27(7), 493-503.
52. Tran, J.Q.; Rana, J.; Barkhof, F.; Melamed, I.; Gevorkyan, H.; Wattjes, M.P.; de Jong, R.; Brosofsky, K.; Ray, S.; Xu, L.; Zhao, J.; Parr, E.; Cadavid, D. Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033. Neurol. Neuroimmunol. Neuroinflamm., 2014, 1(2), e18.
53. Xu, X.; Denic, A.; Warrington, A.E.; Bieber, A.J.; Rodriguez, M. Therapeutics to promote CNS repair: a natural human neuronbinding IgM regulates membrane-raft dynamics and improves motility in a mouse model of multiple sclerosis. J Clin Immunol., 2013, 33(S1), S50-6.
54. Martino, G.; Franklin, R. J.; Baron Van Evercooren, A.; Kerr, D. A. Stem Cells in Multiple Sclerosis Consensus, G., Stem cell transplantation in multiple sclerosis: current status and future prospects. Nature reviews. Neurology, 2010, 6(5), 247-55.
55. Rice, C. M.; Kemp, K.; Wilkins, A.; Scolding, N.J. Cell therapy for multiple sclerosis: an evolving concept with implications for other neurodegenerative diseases. Lancet, 2013, 382(9899), 1204-13.
56. Laterza, C.; Merlini, A.; De Feo, D.; Ruffini, F.; Menon, R.; Onorati, M.; Fredrickx, E.; Muzio, L.; Lombardo, A.; Comi, G.; Quattrini, A.; Taveggia, C.; Farina, C.; Cattaneo, E.; Martino, G. iPSC-derived neural precursors exert a neuroprotective role in immune- mediated demyelination via the secretion of LIF. Nat. Commun., 2013, 4, 2597.
57. Chiurchiu, V.; Maccarrone, M. Chronic inflammatory disorders and their redox control: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal., 2011, 15(9), 2605-41.
58. Witte, M.E.; Mahad, D.J.; Lassmann, H.; van Horssen, J. Mitochondrial dysfunction contributes to neurodegeneration in multiple sclerosis. Trends Mol. Med., 2014, 20(3), 179-87.
59. Carvalho, A.N.; Lim, J.L.; Nijland, P.G.; Witte, M.E.; Van Horssen, J. Glutathione in multiple sclerosis: More than just an antioxidant? Mult. Scler., 2014, May 19, 1352458514533400. [Epub ahead of print] doi: 10.1177/1352458514533400
60. van Horssen, J.; Schreibelt, G.; Drexhage, J.; Hazes, T.; Dijkstra, C. D.; van der Valk, P.; de Vries, H. E. Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radical Biol. Med., 2008, 45(12), 1729-37.
61. Leppert, D.; Waubant, E.; Galardy, R.; Bunnett, N. W.; Hauser, S. L. T cell gelatinases mediate basement membrane transmigration in vitro. J. Immunol., 1995, 154(9), 4379-89.
62. Ortiz, G.G.; Pacheco-Moises, F.P.; Bitzer-Quintero, O.K.; Ramirez- Anguiano, A.C.; Flores-Alvarado, L.J.; Ramirez-Ramirez, V.; Macias-Islas, M. A.; Torres-Sanchez, E. D. Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin. Dev. Immunol., 2013, 2013, 708659.
63. Mahler, A.; Steiniger, J.; Bock, M.; Brandt, A. U.; Haas, V.; Boschmann, M.; Paul, F. Is metabolic flexibility altered in multiple sclerosis patients? PloS One, 2012, 7(8), e43675.
64. von Geldern, G.; Mowry, E. M. The influence of nutritional factors on the prognosis of multiple sclerosis. Nature reviews. Neurology, 2012, 8(12), 678-89.
65. Gonsette, R.E.; Sindic, C.; D'Hooghe, M.B.; De Deyn, P.P.; Medaer, R.; Michotte, A.; Seeldrayers, P.; Guillaume, D.; group, A.S. Boosting endogenous neuroprotection in multiple sclerosis: the ASsociation of Inosine and Interferon beta in relapsing- remitting Multiple Sclerosis (ASIIMS) trial. Mult. Scler., 2010, 16(4), 455-62.
66. Lovera, J.F.; Kim, E.; Heriza, E.; Fitzpatrick, M.; Hunziker, J.; Turner, A. P.; Adams, J.; Stover, T.; Sangeorzan, A.; Sloan, A.; Howieson, D.; Wild, K.; Haselkorn, J.; Bourdette, D. Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial. Neurology, 2012, 79(12), 1278-84.
67. Khalili, M.; Azimi, A.; Izadi, V.; Eghtesadi, S.; Mirshafiey, A.; Sahraian, M.A.; Motevalian, A.; Norouzi, A.; Sanoobar, M.; Eskandari, G.; Farhoudi, M.; Amani, F. Does Lipoic Acid Consumption Affect the Cytokine Profile in Multiple Sclerosis Patients: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. Neuroimmunomodulation, 2014, May 6 [Epub ahead of print] doi:10.1159/000356145
68. Becker, C.; Bray-French, K.; Drewe, J. Pharmacokinetic evaluation of idebenone. Exp. Opin. Drug Metab. Toxicol., 2010, 6(11), 1437- 44.
69. Yadav, V.; Bourdette, D. Oral disease-modifying therapies for multiple sclerosis: are we there yet? Curr. Neurol. Neurosci. Rep., 2010, 10(5), 333-5.
70. Phillips, J.T.; Fox, R.J. BG-12 in multiple sclerosis. Semin. Neurol., 2013, 33(1), 56-65.
71. Ruggieri, S.; Tortorella, C.; Gasperini, C. Pharmacology and clinical efficacy of dimethyl fumarate (BG-12) for treatment of relapsing- remitting multiple sclerosis. Ther. Clin. Risk Manag., 2014, 10, 229-239.
72. 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(2) e00055
73. Fox, R.J.; Kita, M.; Cohan, S.L.; Henson, L.J.; Zambrano, J.; Scannevin, R. H. O'Gorman, J.; Novas, M.; Dawson, K. T.; Phillips, J. T., BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr. Med. Res. Opin., 2014, 30(2), 251-62.
74. Fox, R.J.; Miller, D.H.; Phillips, J.T.; Hutchinson, M.; Havrdova, E.; Kita, M.; Yang, M.; Raghupathi, K.; Novas, M.; Sweetser, M.T.; Viglietta, V.; Dawson, K. T. Investigators, C. S., Placebocontrolled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N. Engl. J. Med., 2012, 367(12), 1087-97.
75. Gold, R.; Kappos, L.; Arnold, D. L.; Bar-Or, A.; Giovannoni, G.; Selmaj, K.; Tornatore, C.; Sweetser, M. T.; Yang, M.; Sheikh, S. I.; Dawson, K. T.; Investigators, D. S. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N. Engl. J. Med., 2012, 367(12), 1098-107.
76. Ramirez-Ramirez, V.; Macias-Islas, M.A.; Ortiz, G.G.; Pacheco- Moises, F.; Torres-Sanchez, E.D.; Sorto-Gomez, T.E.; Cruz- Ramos, J.A.; Orozco-Avina, G.; Celis de la Rosa, A. J. Efficacy of fish oil on serum of TNF alpha, IL-1 beta, and IL-6 oxidative stress markers in multiple sclerosis treated with interferon beta-1b. Oxid. Med. Cell Longev., 2013, 2013, 709493.
77. Noubade, R.; Wong, K.; Ota, N.; Rutz, S.; Eidenschenk, C.; Valdez, P.A.; Ding, J.; Peng, I.; Sebrell, A.; Caplazi, P.; DeVoss, J.; Soriano, R.H.; Sai, T.; Lu, R.; Modrusan, Z.; Hackney, J.; Ouyang, W. NRROS negatively regulates reactive oxygen species during host defence and autoimmunity. Nature, 2014, 509(7499). 235-9.