Skip to main content
SpringerLink
Log in

A Further TWEAK to Multiple Sclerosis Pathophysiology

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF super family that controls many cellular activities including proliferation, migration, differentiation, apoptosis, and inflammation by binding to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell surface receptor. Recent studies have indicated that TWEAK–Fn14 axis signaling may contribute to chronic autoimmune diseases. TWEAK expression via microglia in cortical lesions, presence of TWEAK+ macrophages in inflamed leptomeninges, and absence of TWEAK/Fn14 expression in healthy brain implicates importance of this pathway in pathogenesis of multiple sclerosis lesions. TWEAK–Fn14 axis blockade has also shown promise in various multiple sclerosis animal models. Stimulation of the TWEAK/Fn14 pathway can result in activation of both canonical and noncanonical NF-κB signaling and could also stimulate mitogen-activated protein kinase (MAPK) signaling pathways. Here, we have reviewed evidence of the possible role of TWEAK–Fn14 axis in pathophysiology of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) via neuroinflammation, tissue remodeling, blood–brain barrier (BBB) disruption, neurodegeneration, and astrogliosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Nylander A, Hafler DA (2012) Multiple sclerosis. J Clin Invest 122(4):1180–1188. doi:10.1172/JCI58649

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Lucchinetti CF, Popescu BFG, Bunyan RF, Moll NM, Roemer SF, Lassmann H, Brück W, Parisi JE, Scheithauer BW, Giannini C (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365(23):2188–2197

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Perper SJ, Browning B, Burkly LC, Weng S, Gao C, Giza K, Su L, Tarilonte L, Crowell T, Rajman L (2006) TWEAK is a novel arthritogenic mediator. J Immunol 177(4):2610–2620

    CAS  PubMed  Google Scholar 

  4. Kamata K, Kamijo S, Nakajima A, Koyanagi A, Kurosawa H, Yagita H, Okumura K (2006) Involvement of TNF-like weak inducer of apoptosis in the pathogenesis of collagen-induced arthritis. J Immunol 177(9):6433–6439

    CAS  PubMed  Google Scholar 

  5. Michaelson JS, Wisniacki N, Burkly LC, Putterman C (2012) Role of TWEAK in lupus nephritis: a bench-to-bedside review. Journal of Autoimmunity

  6. Dohi T, Burkly LC (2012) The TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases; focus on inflammatory bowel diseases. J Leukoc Biol 92(2):265–279

    Article  CAS  PubMed  Google Scholar 

  7. Blanco-Colio LM, Martin-Ventura JL, Munoz-Garcia B, Moreno JA, Meilhac O, Ortiz A, Egido J (2007) TWEAK and Fn14. New players in the pathogenesis of atherosclerosis. Front Biosci 12:3648–3655

    Article  CAS  PubMed  Google Scholar 

  8. Sanz AB, Sanchez-Niño MD, Ortiz A (2011) TWEAK, a multifunctional cytokine in kidney injury. Kidney international

  9. Kumar A, Bhatnagar S, Paul PK (2012) TWEAK and TRAF6 regulate skeletal muscle atrophy. Current Opinion in Clinical Nutrition & Metabolic Care 15(3):233

    Article  CAS  Google Scholar 

  10. Winkles JA, Tran NL, Berens ME (2006) TWEAK and Fn14: new molecular targets for cancer therapy? Cancer Lett 235(1):11–17

    Article  CAS  PubMed  Google Scholar 

  11. Chicheportiche Y, Bourdon PR, Xu H, Hsu YM, Scott H, Hession C, Garcia I, Browning JL (1997) TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem 272(51):32401–32410

    Article  CAS  PubMed  Google Scholar 

  12. Maecker H, Varfolomeev E, Kischkel F, Lawrence D, LeBlanc H, Lee W, Hurst S, Danilenko D, Li J, Filvaroff E, Yang B, Daniel D, Ashkenazi A (2005) TWEAK attenuates the transition from innate to adaptive immunity. Cell 123(5):931–944. doi:10.1016/j.cell.2005.09.022

    Article  CAS  PubMed  Google Scholar 

  13. Burkly LC, Michaelson JS, Zheng TS (2011) TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses. Immunol Rev 244(1):99–114. doi:10.1111/j.1600-065X.2011.01054.x

    Article  CAS  PubMed  Google Scholar 

  14. Desplat-Jego S, Varriale S, Creidy R, Terra R, Bernard D, Khrestchatisky M, Izui S, Chicheportiche Y, Boucraut J (2002) TWEAK is expressed by glial cells, induces astrocyte proliferation and increases EAE severity. J Neuroimmunol 133(1–2):116–123

    Article  CAS  PubMed  Google Scholar 

  15. Nakayama M, Kayagaki N, Yamaguchi N, Okumura K, Yagita H (2000) Involvement of TWEAK in Interferon γ-stimulated monocyte cytotoxicity. The Journal of experimental medicine 192(9):1373–1380

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Winkles JA (2008) The TWEAK–Fn14 cytokine–receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov 7(5):411–425. doi:10.1038/nrd2488

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Bossen C, Ingold K, Tardivel A, Bodmer JL, Gaide O, Hertig S, Ambrose C, Tschopp J, Schneider P (2006) Interactions of tumor necrosis factor (TNF) and TNF receptor family members in the mouse and human. J Biol Chem 281(20):13964–13971. doi:10.1074/jbc.M601553200

    Article  CAS  PubMed  Google Scholar 

  18. Wiley SR, Cassiano L, Lofton T, Davis-Smith T, Winkles JA, Lindner V, Liu H, Daniel TO, Smith CA, Fanslow WC (2001) A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity 15(5):837–846

    Article  CAS  PubMed  Google Scholar 

  19. Potrovita I, Zhang W, Burkly L, Hahm K, Lincecum J, Wang MZ, Maurer MH, Rossner M, Schneider A, Schwaninger M (2004) Tumor necrosis factor-like weak inducer of apoptosis-induced neurodegeneration. J Neurosci 24(38):8237–8244

    Article  CAS  PubMed  Google Scholar 

  20. Burkly LC, Michaelson JS, Hahm K, Jakubowski A, Zheng TS (2007) TWEAKing tissue remodeling by a multifunctional cytokine: role of TWEAK/Fn14 pathway in health and disease. Cytokine 40(1):1–16. doi:10.1016/j.cyto.2007.09.007

    Article  CAS  PubMed  Google Scholar 

  21. Girgenrath M, Weng S, Kostek CA, Browning B, Wang M, Brown SA, Winkles JA, Michaelson JS, Allaire N, Schneider P (2006) TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. EMBO J 25(24):5826–5839

    Article  CAS  PubMed  Google Scholar 

  22. Jakubowski A, Ambrose C, Parr M, Lincecum JM, Wang MZ, Zheng TS, Browning B, Michaelson JS, Baestcher M, Wang B (2005) TWEAK induces liver progenitor cell proliferation. J Clin Invest 115(9):2330–2340

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Brown SA, Hanscom HN, Vu H, Brew SA, Winkles JA (2006) TWEAK binding to the Fn14 cysteine-rich domain depends on charged residues located in both the A1 and D2 modules. Biochem J 397(2):297–304. doi:10.1042/BJ20051362

    Article  CAS  PubMed  Google Scholar 

  24. Saitoh T, Nakayama M, Nakano H, Yagita H, Yamamoto N, Yamaoka S (2003) TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation. J Biol Chem 278(38):36005–36012. doi:10.1074/jbc.M304266200

    Article  CAS  PubMed  Google Scholar 

  25. Bover LC, Cardo-Vila M, Kuniyasu A, Sun J, Rangel R, Takeya M, Aggarwal BB, Arap W, Pasqualini R (2007) A previously unrecognized protein–protein interaction between TWEAK and CD163: potential biological implications. J Immunol 178(12):8183–8194

    CAS  PubMed  Google Scholar 

  26. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law SK, Moestrup SK (2001) Identification of the haemoglobin scavenger receptor. Nature 409(6817):198–201. doi:10.1038/35051594

    Article  CAS  PubMed  Google Scholar 

  27. Moreno JA, Munoz-Garcia B, Martin-Ventura JL, Madrigal-Matute J, Orbe J, Paramo JA, Ortega L, Egido J, Blanco-Colio LM (2009) The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. Atherosclerosis 207(1):103–110. doi:10.1016/j.atherosclerosis.2009.04.033

    Article  CAS  PubMed  Google Scholar 

  28. Fick A, Lang I, Schäfer V, Seher A, Trebing J, Weisenberger D, Wajant H (2012) Studies of binding of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to fibroblast growth factor inducible 14 (Fn14). J Biol Chem 287(1):484–495

    Article  CAS  PubMed  Google Scholar 

  29. Yepes M (2007) TWEAK and the central nervous system. Mol Neurobiol 35(3):255–265

    Article  CAS  PubMed  Google Scholar 

  30. Constantinescu CS, Farooqi N, O'Brien K, Gran B (2011) Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 164(4):1079–1106. doi:10.1111/j.1476-5381.2011.01302.x

    Article  CAS  PubMed  Google Scholar 

  31. Desplat-Jego S, Creidy R, Varriale S, Allaire N, Luo Y, Bernard D, Hahm K, Burkly L, Boucraut J (2005) Anti-TWEAK monoclonal antibodies reduce immune cell infiltration in the central nervous system and severity of experimental autoimmune encephalomyelitis. Clin Immunol 117(1):15–23. doi:10.1016/j.clim.2005.06.005

    Article  CAS  PubMed  Google Scholar 

  32. Mueller AM, Pedre X, Kleiter I, Hornberg M, Steinbrecher A, Giegerich G (2005) Targeting fibroblast growth factor-inducible-14 signaling protects from chronic relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol 159(1–2):55–65. doi:10.1016/j.jneuroim.2004.10.001

    Article  CAS  PubMed  Google Scholar 

  33. Kipp M, Clarner T, Dang J, Copray S, Beyer C (2009) The cuprizone animal model: new insights into an old story. Acta neuropathologica 118(6):723–736

    Article  PubMed  Google Scholar 

  34. Iocca HA, Plant SR, Wang Y, Runkel L, O'Connor BP, Lundsmith ET, Hahm K, van Deventer HW, Burkly LC, Ting JP (2008) TNF superfamily member TWEAK exacerbates inflammation and demyelination in the cuprizone-induced model. J Neuroimmunol 194(1–2):97–106. doi:10.1016/j.jneuroim.2007.12.003

    Article  CAS  PubMed  Google Scholar 

  35. Razmara M, Hilliard B, Ziarani AK, Murali R, Yellayi S, Ghazanfar M, Chen YH, Tykocinski ML (2009) Fn14-TRAIL, a chimeric intercellular signal exchanger, attenuates experimental autoimmune encephalomyelitis. Am J Pathol 174(2):460–474. doi:10.2353/ajpath.2009.080462

    Article  CAS  PubMed  Google Scholar 

  36. Prinz-Hadad H, Mizrachi T, Irony-Tur-Sinai M, Prigozhina TB, Aronin A, Brenner T, Dranitzki-Elhalel M (2013) Amelioration of autoimmune neuroinflammation by the fusion molecule Fn14.TRAIL. J Neuroinflammation 10:36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Desplat-Jego S, Feuillet L, Creidy R, Malikova I, Rance R, Khrestchatisky M, Hahm K, Burkly LC, Pelletier J, Boucraut J (2009) TWEAK is expressed at the cell surface of monocytes during multiple sclerosis. J Leukoc Biol 85(1):132–135. doi:10.1189/jlb.0608347

    Article  CAS  PubMed  Google Scholar 

  38. Burkly LC, Dohi T (2011) The TWEAK/Fn14 pathway in tissue remodeling: for better or for worse. Adv Exp Med Biol 691:305–322. doi:10.1007/978-1-4419-6612-4_32

    Article  CAS  PubMed  Google Scholar 

  39. Serafini B, Magliozzi R, Rosicarelli B, Reynolds R, Zheng TS, Aloisi F (2008) Expression of TWEAK and its receptor Fn14 in the multiple sclerosis brain: implications for inflammatory tissue injury. J Neuropathol Exp Neurol 67(12):1137–1148. doi:10.1097/NEN.0b013e31818dab90

    Article  PubMed  Google Scholar 

  40. Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ (2003) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62(7):723–732

    PubMed  Google Scholar 

  41. Calabrese M, Filippi M, Gallo P (2010) Cortical lesions in multiple sclerosis. Nat Rev Neurol 6(8):438–444. doi:10.1038/nrneurol.2010.93

    Article  PubMed  Google Scholar 

  42. Kutzelnigg A, Lassmann H (2006) Cortical demyelination in multiple sclerosis: a substrate for cognitive deficits? J Neurol Sci 245(1–2):123–126. doi:10.1016/j.jns.2005.09.021

    Article  PubMed  Google Scholar 

  43. Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M, Reynolds R, Aloisi F (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130(Pt 4):1089–1104. doi:10.1093/brain/awm038

    PubMed  Google Scholar 

  44. Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128(Pt 11):2705–2712. doi:10.1093/brain/awh641

    Article  PubMed  Google Scholar 

  45. Harada N, Nakayama M, Nakano H, Fukuchi Y, Yagita H, Okumura K (2002) Pro-inflammatory effect of TWEAK/Fn14 interaction on human umbilical vein endothelial cells. Biochem Biophys Res Commun 299(3):488–493

    Article  CAS  PubMed  Google Scholar 

  46. Saas P, Boucraut J, Walker PR, Quiquerez AL, Billot M, Desplat-Jego S, Chicheportiche Y, Dietrich PY (2000) TWEAK stimulation of astrocytes and the proinflammatory consequences. Glia 32(1):102–107. doi:10.1002/1098-1136(200010)32:1<102::AID-GLIA100>3.0.CO;2-U

    Article  CAS  PubMed  Google Scholar 

  47. Stephan D, Sbai O, Wen J, Couraud PO, Putterman C, Khrestchatisky M, Desplat-Jego S (2013) TWEAK/Fn14 pathway modulates properties of a human microvascular endothelial cell model of blood brain barrier. J Neuroinflammation 10:9. doi:10.1186/1742-2094-10-9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Yong VW, Power C, Forsyth P, Edwards DR (2001) Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci 2(7):502–511. doi:10.1038/35081571

    Article  CAS  PubMed  Google Scholar 

  49. Yong VW (2005) Metalloproteinases: mediators of pathology and regeneration in the CNS. Nat Rev Neurosci 6(12):931–944. doi:10.1038/nrn1807

    Article  CAS  PubMed  Google Scholar 

  50. Lee MA, Palace J, Stabler G, Ford J, Gearing A, Miller K (1999) Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis. A longitudinal clinical and MRI study. Brain 122(Pt 2):191–197

    Article  PubMed  Google Scholar 

  51. Boz C, Ozmenoglu M, Velioglu S, Kilinc K, Orem A, Alioglu Z, Altunayoglu V (2006) Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with relapsing-remitting multiple sclerosis treated with interferon beta. Clin Neurol Neurosurg 108(2):124–128. doi:10.1016/j.clineuro.2005.01.005

    Article  PubMed  Google Scholar 

  52. Gray E, Thomas TL, Betmouni S, Scolding N, Love S (2008) Elevated matrix metalloproteinase-9 and degradation of perineuronal nets in cerebrocortical multiple sclerosis plaques. J Neuropathol Exp Neurol 67(9):888

    Article  PubMed  Google Scholar 

  53. Cossins JA, Clements JM, Ford J, Miller KM, Pigott R, Vos W, Van der Valk P, De Groot CJ (1997) Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol 94(6):590–598

    Article  CAS  PubMed  Google Scholar 

  54. Dubois B, Masure S, Hurtenbach U, Paemen L, Heremans H, van den Oord J, Sciot R, Meinhardt T, Hammerling G, Opdenakker G, Arnold B (1999) Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. J Clin Invest 104(11):1507–1515. doi:10.1172/JCI6886

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Avolio C, Filippi M, Tortorella C, Rocca MA, Ruggieri M, Agosta F, Tomassini V, Pozzilli C, Stecchi S, Giaquinto P, Livrea P, Trojano M (2005) Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment. Mult Scler 11(4):441–446

    Article  CAS  PubMed  Google Scholar 

  56. Kim SH, Kang YJ, Kim WJ, Woo DK, Lee Y, Kim DI, Park YB, Kwon BS, Park JE, Lee WH (2004) TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Circ J 68(4):396–399

    Article  CAS  PubMed  Google Scholar 

  57. Polavarapu R, Gongora MC, Winkles JA, Yepes M (2005) Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappa B pathway activation. J Neurosci 25(44):10094–10100. doi:10.1523/JNEUROSCI.3382-05.2005

    Article  CAS  PubMed  Google Scholar 

  58. Zhang X, Winkles JA, Gongora MC, Polavarapu R, Michaelson JS, Hahm K, Burkly L, Friedman M, Li XJ, Yepes M (2007) TWEAK–Fn14 pathway inhibition protects the integrity of the neurovascular unit during cerebral ischemia. J Cereb Blood Flow Metab 27(3):534–544. doi:10.1038/sj.jcbfm.9600368

    Article  PubMed  Google Scholar 

  59. Li H, Mittal A, Paul PK, Kumar M, Srivastava DS, Tyagi SC, Kumar A (2009) Tumor necrosis factor-related weak inducer of apoptosis augments matrix metalloproteinase 9 (MMP-9) production in skeletal muscle through the activation of nuclear factor-kappaB-inducing kinase and p38 mitogen-activated protein kinase: a potential role of MMP-9 in myopathy. J Biol Chem 284(7):4439–4450. doi:10.1074/jbc.M805546200

    Article  CAS  PubMed  Google Scholar 

  60. Moore CS, Abdullah SL, Brown A, Arulpragasam A, Crocker SJ (2011) How factors secreted from astrocytes impact myelin repair. J Neurosci Res 89(1):13–21. doi:10.1002/jnr.22482

    Article  CAS  PubMed  Google Scholar 

  61. Williams A, Piaton G, Lubetzki C (2007) Astrocytes—friends or foes in multiple sclerosis? Glia 55(13):1300–1312. doi:10.1002/glia.20546

    Article  PubMed  Google Scholar 

  62. Nair A, Frederick T, Miller S (2008) Astrocytes in multiple sclerosis: a product of their environment. Cellular and Molecular Life Sciences 65(17):2702–2720. doi:10.1007/s00018-008-8059-5

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Zamanian JL, Xu L, Foo LC, Nouri N, Zhou L, Giffard RG, Barres BA (2012) Genomic analysis of reactive astrogliosis. J Neurosci 32(18):6391–6410. doi:10.1523/jneurosci.6221-11.2012

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Rousselet E, Traver S, Monnet Y, Perrin A, Mandjee N, Hild A, Hirsch EC, Zheng TS, Hunot S (2012) Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) induces astrocyte proliferation through the activation of transforming growth factor (TGF)-α/epidermal growth factor receptor (EGFR) signaling pathway. Mol Pharmacol. doi:10.1124/mol.112.079608

    PubMed  Google Scholar 

  65. Mc Guire C, Beyaert R, van Loo G (2011) Death receptor signalling in central nervous system inflammation and demyelination. Trends Neurosci 34(12):619–628. doi:10.1016/j.tins.2011.09.002

    Article  CAS  PubMed  Google Scholar 

  66. Haile WB, Echeverry R, Wu F, Guzman J, An J, Wu J, Yepes M (2010) Tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 mediate cerebral ischemia-induced poly(ADP-ribose) polymerase-1 activation and neuronal death. Neuroscience 171(4):1256–1264. doi:10.1016/j.neuroscience.2010.10.029

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Nakayama M, Ishidoh K, Kayagaki N, Kojima Y, Yamaguchi N, Nakano H, Kominami E, Okumura K, Yagita H (2002) Multiple pathways of TWEAK-induced cell death. J Immunol 168(2):734–743

    CAS  PubMed  Google Scholar 

  68. Wang D, Fung JN, Tuo Y, Hu L, Chen C (2010) TWEAK/Fn14 promotes apoptosis of human endometrial cancer cells via caspase pathway. Cancer Lett 294(1):91–100. doi:10.1016/j.canlet.2010.01.027

    Article  CAS  PubMed  Google Scholar 

  69. Justo P, Sanz AB, Sanchez-Nino MD, Winkles JA, Lorz C, Egido J, Ortiz A (2006) Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int 70(10):1750–1758. doi:10.1038/sj.ki.5001866

    Article  CAS  PubMed  Google Scholar 

  70. Bhatnagar S, Mittal A, Gupta SK, Kumar A (2012) TWEAK causes myotube atrophy through coordinated activation of ubiquitin-proteasome system, autophagy, and caspases. J Cell Physiol 227(3):1042–1051

    Article  CAS  PubMed  Google Scholar 

  71. Yu SW, Wang H, Poitras MF, Coombs C, Bowers WJ, Federoff HJ, Poirier GG, Dawson TM, Dawson VL (2002) Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor. Science 297(5579):259–263. doi:10.1126/science.1072221

    Article  CAS  PubMed  Google Scholar 

  72. Cavone L, Aldinucci A, Ballerini C, Biagioli T, Moroni F, Chiarugi A (2011) PARP-1 inhibition prevents CNS migration of dendritic cells during EAE, suppressing the encephalitogenic response and relapse severity. Mult Scler 17(7):794–807. doi:10.1177/1352458511399113

    Article  PubMed  Google Scholar 

  73. Chiarugi A (2002) Inhibitors of poly(ADP-ribose) polymerase-1 suppress transcriptional activation in lymphocytes and ameliorate autoimmune encephalomyelitis in rats. Br J Pharmacol 137(6):761–770. doi:10.1038/sj.bjp.0704934

    Article  CAS  PubMed  Google Scholar 

  74. Scott GS, Kean RB, Mikheeva T, Fabis MJ, Mabley JG, Szabo C, Hooper DC (2004) The therapeutic effects of PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation. J Pharmacol Exp Ther 310(3):1053–1061. doi:10.1124/jpet.103.063214

    Article  CAS  PubMed  Google Scholar 

  75. Farez MF, Quintana FJ, Gandhi R, Izquierdo G, Lucas M, Weiner HL (2009) Toll-like receptor 2 and poly(ADP-ribose) polymerase 1 promote central nervous system neuroinflammation in progressive EAE. Nat Immunol 10(9):958–964. doi:10.1038/ni.1775

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Echeverry R, Wu F, Haile WB, Wu J, Yepes M (2012) The cytokine tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 have a neuroprotective effect in the central nervous system. J Neuroinflammation 9:45. doi:10.1186/1742-2094-9-45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. van Oosten BW, Barkhof F, Truyen L, Boringa JB, Bertelsmann FW, von Blomberg BM, Woody JN, Hartung HP, Polman CH (1996) Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47(6):1531–1534

    Article  PubMed  Google Scholar 

  78. TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group (1999) Neurology 53(3):457–465

    Article  Google Scholar 

  79. Michaelson JS, Wisniacki N, Burkly LC, Putterman C (2012) Role of TWEAK in lupus nephritis: a bench-to-bedside review. J Autoimmun 39(3):130–142. doi:10.1016/j.jaut.2012.05.003

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Wisniacki N, Chindalore VL, Codding CE, Greenwald MW, Shaw ML, Fitilev S, Ershova O, Hu X, Zheng TS, Amaravadi L A Phase I, randomized, double-blind, placebo-controlled, single dose, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of BIIB023 (anti-TWEAK) in subjects with rheumatoid arthritis. In: Arthritis and rheumatism, 2011. Wiley-Blackwell, MALDEN, pp S858-S858

  81. Yepes M, Brown SA, Moore EG, Smith EP, Lawrence DA, Winkles JA (2005) A soluble Fn14-Fc decoy receptor reduces infarct volume in a murine model of cerebral ischemia. Am J Pathol 166(2):511–520. doi:10.1016/S0002-9440(10)62273-0

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

AN & PH wish to express their gratitude to the Multiple Sclerosis International Federation (MSIF) for the opportunity to visit the Montreal Neurological Institute.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Interdisciplinary Neuroscience Research Program, Tehran University of Medical Sciences, Tehran, Iran

    Arash Nazeri, Pouria Heydarpour & Shokufeh Sadaghiani

  2. Sina MS Research Center, Department of Neurology, Tehran University of Medical Sciences, Tehran, Iran

    Arash Nazeri, Pouria Heydarpour, Shokufeh Sadaghiani & Mohammad Ali Sahraian

  3. Immunology Discovery Research, Biogen Idec, Inc, Cambridge, MA, USA

    Linda C. Burkly

  4. Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada

    Amit Bar-Or

Authors
  1. Arash Nazeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pouria Heydarpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shokufeh Sadaghiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Ali Sahraian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Linda C. Burkly
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amit Bar-Or
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amit Bar-Or.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nazeri, A., Heydarpour, P., Sadaghiani, S. et al. A Further TWEAK to Multiple Sclerosis Pathophysiology. Mol Neurobiol 49, 78–87 (2014). https://doi.org/10.1007/s12035-013-8490-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-013-8490-y

Keywords

Search

Navigation