Sphingosine-1 phosphate and central nervous system

Current Topics in Microbiology and Immunology

Volumn 378, Issue , 2014, Pages 149-170

  Martin, Roland ^a   Sospedra, Mireia ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

BETA INTERFERON; FINGOLIMOD; SPHINGOSINE 1 PHOSPHATE; SPHINGOSINE 1 PHOSPHATE RECEPTOR; DRUG DERIVATIVE; LYSOPHOSPHOLIPID; SPHINGOSINE; SPHINGOSINE 1-PHOSPHATE;

ADVERSE OUTCOME; ARTICLE; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN BLOOD FLOW; CELL POPULATION; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM; CENTRAL NERVOUS SYSTEM FUNCTION; CENTRAL NERVOUS SYSTEM TUMOR; ENDOTHELIUM CELL; HUMAN; IMMUNOMODULATION; IMMUNOPATHOLOGY; MICROGLIA; MULTIPLE SCLEROSIS; MYELINATION; NERVE CELL; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REMYELINIZATION; SIGNAL TRANSDUCTION; ANIMAL; CENTRAL NERVOUS SYSTEM DISEASE; DRUG POTENTIATION; METABOLISM; REVIEW;

ANIMALS; CENTRAL NERVOUS SYSTEM DISEASES; HUMANS; LYSOPHOSPHOLIPIDS; RECEPTORS, LYSOSPHINGOLIPID; SPHINGOSINE;

EID: 84904267919     PISSN: 0070217X     EISSN: 21969965     Source Type: Book Series    
DOI: 10.1007/978-3-319-05879-5_7     Document Type: Article

References (116)

1. Akahoshi N, Ishizaki Y, Yasuda H, Murashima YL, Shinba T, Goto K, Himi T, Chun J, Ishii I (2011) Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2. Epilepsy Behav 22: 659-665.
2. Ascherio A, Munger K (2008) Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol 28: 17-28.
3. Barkhof F, Calabresi PA, Miller DH, Reingold SC (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5: 256-266.
4. Bartholomäus I, Schläger C, Brinkmann V, Wekerle H, Flügel A (2008) Intravital 2-photon imaging of encephalitogenic effector cells during fingolimod (FTY720) treatment of experimental autoimmune encephalomyelitis. World Congress on Treatment and Research in Multiple Sclerosis (ECTRIMS), Montreal. Poster P7.
5. Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, Cotsapas C, Shah TS, Spencer C, Booth D, Goris A et al (2013) Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 45: 1353-1360.
6. Benarroch EE (2013) Microglia: multiple roles in surveillance, circuit shaping, and response to injury. Neurology 81: 1079-1088.
7. Bieberich E (2011) There is more to a lipid than just being a fat: sphingolipid-guided differentiation of oligodendroglial lineage from embryonic stem cells. Neurochem Res 36: 1601-1611.
8. Boulton C, Meiser K, David OJ, Schmouder R (2012) Pharmacodynamic effects of steady-state fingolimod on antibody response in healthy volunteers: a 4-week, randomized, placebocontrolled, parallel-group, multiple-dose study. J Clin Pharmacol 52: 1879-1890.
9. Brana C, Frossard MJ, Pescini Gobert R, Martinier N, Boschert U, Seabrook TJ (2013) Immunohistochemical detection of sphingosine-1-phosphate receptor 1 and 5 in human multiple sclerosis lesions. Neuropathol Appl Neurobiol.
10. Brinkmann V (2007) Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther 115: 84-105.
11. Brinkmann V (2009) FTY720 (fingolimod) in multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol 158: 1173-1182.
12. Brinkmann V, Chen S, Feng L, Pinschewer D, Nikolova Z, Hof R (2001) FTY720 alters lymphocyte homing and protects allografts without inducing general immunosuppression. Transplant Proc 33: 530-531.
13. Brinkmann V, Cyster JG, Hla T (2004) FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 4: 1019-1025.
14. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, Francis G, Aradhye S, Burtin P (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9: 883-897.
15. Bryan L, Kordula T, Spiegel S, Milstien S (2008a) Regulation and functions of sphingosine kinases in the brain. Biochim Biophys Acta 1781: 459-466.
16. Bryan L, Paugh BS, Kapitonov D, Wilczynska KM, Alvarez SM, Singh SK, Milstien S, Spiegel S, Kordula T (2008b) Sphingosine-1-phosphate and interleukin-1 independently regulate plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor expression in glioblastoma cells: implications for invasiveness. Mol Cancer Res 6: 1469-1477.
17. Callihan P, Hooks SB (2012) Sphingosine-1-phosphate signaling in neural progenitors. Methods Mol Biol 874: 193-200.
18. Callihan P, Zitomer NC, Stoeling MV, Kennedy PC, Lynch KR, Riley RT, Hooks SB (2012) Distinct generation, pharmacology, and distribution of sphingosine 1-phosphate and dihydrosphingosine 1-phosphate in human neural progenitor cells. Neuropharmacology 62: 988-996.
19. Cannon RE, Peart JC, Hawkins BT, Campos CR, Miller DS (2012) Targeting blood-brain barrier sphingolipid signaling reduces basal P-glycoprotein activity and improves drug delivery to the brain. Proc Natl Acad Sci USA 109: 15930-15935.
20. Chakraborty G, Saito M, Shah R, Mao RF, Vadasz C, Saito M (2012) Ethanol triggers sphingosine 1-phosphate elevation along with neuroapoptosis in the developing mouse brain. J Neurochem 121: 806-817.
21. Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, Noguchi K, Teo ST, Yung YC, Lu M, Kennedy G et al (2011) FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proc Natl Acad Sci USA 108: 751-756.
22. Chun J, Hartung HP (2010) Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol 33: 91-101.
23. Coelho RP, Payne SG, Bittman R, Spiegel S, Sato-Bigbee C (2007) The immunomodulator FTY720 has a direct cytoprotective effect in oligodendrocyte progenitors. J Pharmacol Exp Ther 323: 626-635.
24. Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362: 402-415.
25. Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL et al (2012) Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 380: 1829-1839.
26. Contos JJ, Ishii I, Fukushima N, Kingsbury MA, Ye X, Kawamura S, Brown JH, Chun J (2002) Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa(2). Mol Cell Biol 22: 6921-6929.
27. Deogracias R, Yazdani M, Dekkers MP, Guy J, Ionescu MC, Vogt KE, Barde YA (2012) Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome. Proc Natl Acad Sci USA 109: 14230-14235.
28. Doi Y, Takeuchi H, Horiuchi H, Hanyu T, Kawanokuchi J, Jin S, Parajuli B, Sonobe Y, Mizuno T, Suzumura A (2013) Fingolimod phosphate attenuates oligomeric amyloid beta-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons. PLoS ONE 8: e61988.
29. Dubin AE, Herr DR, Chun J (2010) Diversity of lysophosphatidic acid receptor-mediated intracellular calcium signaling in early cortical neurogenesis. J Neurosci 30: 7300-7309.
30. Durafourt BA, Lambert C, Johnson TA, Blain M, Bar-Or A, Antel JP (2011) Differential responses of human microglia and blood-derived myeloid cells to FTY720. J Neuroimmunol 230: 10-16.
31. Edsall LC, Pirianov GG, Spiegel S (1997) Involvement of sphingosine 1-phosphate in nerve growth factor-mediated neuronal survival and differentiation. J Neurosci 17: 6952-6960.
32. Engelhardt B (2011) Neuroscience. Blood-brain barrier differentiation. Science 334: 1652-1653.
33. Estrada-Bernal A, Palanichamy K, Ray Chaudhury A, van Brocklyn JR (2012) Induction of brain tumor stem cell apoptosis by FTY720: a potential therapeutic agent for glioblastoma. Neuro Oncol 14: 405-415.
34. Fujino M, Funeshima N, Kitazawa Y, Kimura H, Amemiya H, Suzuki S, Li XK (2003) Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. J Pharmacol Exp Ther 305: 70-77.
35. Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI et al (2012) Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 367: 1098-1107.
36. Goldmann T, Prinz M (2013) Role of microglia in CNS autoimmunity. Clin Dev Immunol 2013: 208093.
37. Grigorova IL, Schwab SR, Phan TG, Pham TH, Okada T, Cyster JG (2009) Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat Immunol 10: 58-65.
38. Groves A, Kihara Y, Chun J (2013) Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy. J Neurol Sci 328: 9-18.
39. Haghikia A, Hohlfeld R, Gold R, Fugger L (2013) Therapies for multiple sclerosis: translational achievements and outstanding needs. Trends Mol Med 19: 309-319.
40. Hasegawa Y, Suzuki H, Sozen T, Rolland W, Zhang JH (2010) Activation of sphingosine 1-phosphate receptor-1 by FTY720 is neuroprotective after ischemic stroke in rats. Stroke 41: 368-374.
41. Hohlfeld R, Barkhof F, Polman C (2011) Future clinical challenges in multiple sclerosis: relevance to sphingosine 1-phosphate receptor modulator therapy. Neurology 76: S28-S37.
42. Ishii I, Ye X, Friedman B, Kawamura S, Contos JJ, Kingsbury MA, Yang AH, Zhang G, Brown JH, Chun J (2002) Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3. J Biol Chem 277: 25152-25159.
43. Jackson SJ, Giovannoni G, Baker D (2011) Fingolimod modulates microglial activation to augment markers of remyelination. J Neuroinflammation 8: 76.
44. Jaillard C, Harrison S, Stankoff B, Aigrot MS, Calver AR, Duddy G, Walsh FS, Pangalos MN, Arimura N, Kaibuchi K et al (2005) Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci 25: 1459-1469.
45. Johnson TA, Evans BL, Durafourt BA, Blain M, Lapierre Y, Bar-Or A, Antel JP (2011) Reduction of the peripheral blood CD56(bright) NK lymphocyte subset in FTY720-treated multiple sclerosis patients. J Immunol 187: 570-579.
46. Jung CG, Kim HJ, Miron VE, Cook S, Kennedy TE, Foster CA, Antel JP, Soliven B (2007) Functional consequences of S1P receptor modulation in rat oligodendroglial lineage cells. Glia 55: 1656-1667.
47. Kajimoto T, Okada T, Yu H, Goparaju SK, Jahangeer S, Nakamura S (2007) Involvement of sphingosine-1-phosphate in glutamate secretion in hippocampal neurons. Mol Cell Biol 27: 3429-3440.
48. Kappos L, Radue EW, O'Connor P, Polman C, Hohlfeld R, Calabresi P, Selmaj K, Agoropoulou C, Leyk M, Zhang-Auberson L et al (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362: 387-401.
49. Kataoka H, Sugahara K, Shimano K, Teshima K, Koyama M, Fukunari A, Chiba K (2005) FTY720, sphingosine 1-phosphate receptor modulator, ameliorates experimental autoimmune encephalomyelitis by inhibition of T cell infiltration. Cell Mol Immunol 2: 439-448.
50. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M, Giuliani F, Arbour N, Becher B, Prat A (2007) Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13: 1173-1175.
51. Kim HJ, Miron VE, Dukala D, Proia RL, Ludwin SK, Traka M, Antel JP, Soliven B (2011) Neurobiological effects of sphingosine 1-phosphate receptor modulation in the cuprizone model. FASEB J 25: 1509-1518.
52. Kimura A, Ohmori T, Ohkawa R, Madoiwa S, Mimuro J, Murakami T, Kobayashi E, Hoshino Y, Yatomi Y, Sakata Y (2007) Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 25: 115-124.
53. Kimura A, Ohmori T, Kashiwakura Y, Ohkawa R, Madoiwa S, Mimuro J, Shimazaki K, Hoshino Y, Yatomi Y, Sakata Y (2008) Antagonism of sphingosine 1-phosphate receptor-2 enhances migration of neural progenitor cells toward an area of brain. Stroke 39: 3411-3417.
54. Kleinschmidt-DeMasters BK, Miravalle A, Schowinsky J, Corboy J, Vollmer T (2012) Update on PML and PML-IRIS occurring in multiple sclerosis patients treated with natalizumab. J Neuropathol Exp Neurol 71: 604-617.
55. Kono M, Belyantseva IA, Skoura A, Frolenkov GI, Starost MF, Dreier JL, Lidington D, Bolz SS, Friedman TB, Hla T et al (2007) Deafness and stria vascularis defects in S1P2 receptor-null mice. J Biol Chem 282: 10690-10696.
56. Lassmann H (2013) Multiple sclerosis: lessons from molecular neuropathology. Exp Neurol.
57. Lee KD, Chow WN, Sato-Bigbee C, Graf MR, Graham RS, Colello RJ, Young HF, Mathern BE (2009) FTY720 reduces inflammation and promotes functional recovery after spinal cord injury. J Neurotrauma 26: 2335-2344.
58. Lewis ND, Haxhinasto SA, Anderson SM, Stefanopoulos DE, Fogal SE, Adusumalli P, Desai SN, Patnaude LA, Lukas SM, Ryan KR et al (2013) Circulating monocytes are reduced by sphingosine-1-phosphate receptor modulators independently of S1P3. J Immunol 190: 3533-3540.
59. Leypoldt F, Munchau A, Moeller F, Bester M, Gerloff C, Heesen C (2009) Hemorrhaging focal encephalitis under fingolimod (FTY720) treatment: a case report. Neurology 72: 1022-1024.
60. Lovett-Racke AE, Yang Y, Racke MK (2011) Th1 versus Th17: are T cell cytokines relevant in multiple sclerosis? Biochim Biophys Acta 1812: 246-251.
61. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47: 707-717.
62. Mac Lennan AJ, Carney PR, Zhu WJ, Chaves AH, Garcia J, Grimes JR, Anderson KJ, Roper SN, Lee N (2001) An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. Eur J Neurosci 14: 203-209.
63. Matloubian M, Lo CG, Cinamon G, Lesneski MJ, Xu Y, Brinkmann V, Allende ML, Proia RL, Cyster JG (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427: 355-360.
64. Mehling M, Brinkmann V, Antel J, Bar-Or A, Goebels N, Vedrine C, Kristofic C, Kuhle J, Lindberg RL, Kappos L (2008) FTY720 therapy exerts differential effects on T cell subsets in multiple sclerosis. Neurology 71: 1261-1267.
65. Mehling M, Johnson TA, Antel J, Kappos L, Bar-Or A (2011) Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 76: S20-S27.
66. Meno-Tetang GM, Li H, Mis S, Pyszczynski N, Heining P, Lowe P, Jusko WJ (2006) Physiologically based pharmacokinetic modeling of FTY720 (2-amino-2[2-(-4-octylphenyl) ethyl]propane-1, 3-diol hydrochloride) in rats after oral and intravenous doses. Drug Metab Dispos 34: 1480-1487.
67. Metzler B, Gfeller P, Wieczorek G, Li J, Nuesslein-Hildesheim B, Katopodis A, Mueller M, Brinkmann V (2008) Modulation of T cell homeostasis and alloreactivity under continuous FTY720 exposure. Int Immunol 20: 633-644.
68. Michaud J, Im DS, Hla T (2010) Inhibitory role of sphingosine 1-phosphate receptor 2 in macrophage recruitment during inflammation. J Immunol 184: 1475-1483.
69. Miron VE, Schubart A, Antel JP (2008a) Central nervous system-directed effects of FTY720 (fingolimod). J Neurol Sci 274: 13-17.
70. Miron VE, Hall JA, Kennedy TE, Soliven B, Antel JP (2008b) Cyclical and dose-dependent responses of adult human mature oligodendrocytes to fingolimod. Am J Pathol 173: 1143-1152.
71. Miron VE, Ludwin SK, Darlington PJ, Jarjour AA, Soliven B, Kennedy TE, Antel JP (2010) Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slices. Am J Pathol 176: 2682-2694.
72. Miron VE, Durafourt BA, Antel JP, Kennedy TE (2012) Assessment of sphingosine-1-phosphate receptor expression and associated intracellular signaling cascades in primary cells of the human central nervous system. Methods Mol Biol 874: 141-154.
73. Mizugishi K, Yamashita T, Olivera A, Miller GF, Spiegel S, Proia RL (2005) Essential role for sphingosine kinases in neural and vascular development. Mol Cell Biol 25: 11113-11121.
74. Mok SW, Proia RL, Brinkmann V, Mabbott NA (2012) B cell-specific S1PR1 deficiency blocks prion dissemination between secondary lymphoid organs. J Immunol 188: 5032-5040.
75. Mullershausen F, Craveiro LM, Shin Y, Cortes-Cros M, Bassilana F, Osinde M, Wishart WL, Guerini D, Thallmair M, Schwab ME et al (2007) Phosphorylated FTY720 promotes astrocyte migration through sphingosine-1-phosphate receptors. J Neurochem 102: 1151-1161.
76. Nishimura H, Akiyama T, Irei I, Hamazaki S, Sadahira Y (2010) Cellular localization of sphingosine-1-phosphate receptor 1 expression in the human central nervous system. J Histochem Cytochem 58: 847-856.
77. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343: 938-952.
78. Novgorodov AS, El-Alwani M, Bielawski J, Obeid LM, Gudz TI (2007) Activation of sphingosine-1-phosphate receptor S1P5 inhibits oligodendrocyte progenitor migration. FASEB J 21: 1503-1514.
79. O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A et al (2011) Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 365: 1293-1303.
80. Oo ML, Thangada S, Wu MT, Liu CH, Macdonald TL, Lynch KR, Lin CY, Hla T (2007) Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor. J Biol Chem 282: 9082-9089.
81. Oo ML, Chang SH, Thangada S, Wu MT, Rezaul K, Blaho V, Hwang SI, Han DK, Hla T (2011) Engagement of S1P(1)-degradative mechanisms leads to vascular leak in mice. J Clin Invest 121: 2290-2300.
82. Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG et al (2007) Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316: 295-298.
83. Peters A, Lee Y, Kuchroo VK (2011) The many faces of Th17 cells. Curr Opin Immunol 23: 702-706.
84. Pinschewer DD, Ochsenbein AF, Odermatt B, Brinkmann V, Hengartner H, Zinkernagel RM (2000) FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J Immunol 164: 5761-5770.
85. Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A et al (2006) A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 354: 899-910.
86. Rao TS, Lariosa-Willingham KD, Lin FF, Palfreyman EL, Yu N, Chun J, Webb M (2003) Pharmacological characterization of lysophospholipid receptor signal transduction pathways in rat cerebrocortical astrocytes. Brain Res 990: 182-194.
87. Rau CR, Hein K, Sattler MB, Kretzschmar B, Hillgruber C, McRae BL, Diem R, Bahr M (2011) Anti-inflammatory effects of FTY720 do not prevent neuronal cell loss in a rat model of optic neuritis. Am J Pathol 178: 1770-1781.
88. Ricklin ME, Lorscheider J, Waschbisch A, Paroz C, Mehta SK, Pierson DL, Kuhle J, Fischer-Barnicol B, Sprenger T, Lindberg RL et al (2013) T-cell response against varicella-zoster virus in fingolimod-treated MS patients. Neurology 81: 174-181.
89. Rosado FG, Kim AS (2013) Hemophagocytic lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol 139: 713-727.
90. Rossi S, Lo Giudice T, De Chiara V, Musella A, Studer V, Motta C, Bernardi G, Martino G, Furlan R, Martorana A et al (2012) Oral fingolimod rescues the functional deficits of synapses in experimental autoimmune encephalomyelitis. Br J Pharmacol 165: 861-869.
91. Sallusto F, Zielinski CE, Lanzavecchia A (2012) Human Th17 subsets. Eur J Immunol 42: 2215-2220.
92. Sim-Selley LJ, Goforth PB, Mba MU, Macdonald TL, Lynch KR, Milstien S, Spiegel S, Satin LS, Welch SP, Selley DE (2009) Sphingosine-1-phosphate receptors mediate neuromodulatory functions in the CNS. J Neurochem 110: 1191-1202.
93. Sinha RK, Park C, Hwang IY, Davis MD, Kehrl JH (2009) B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis. Immunity 30: 434-446.
94. Sorensen SD, Nicole O, Peavy RD, Montoya LM, Lee CJ, Murphy TJ, Traynelis SF, Hepler JR (2003) Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol Pharmacol 64: 1199-1209.
95. Sospedra M, Martin R (2005) Immunology of multiple sclerosis. Annu Rev Immunol 23: 683-747.
96. Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4: 397-407.
97. Stone LA, Smith ME, Albert PS, Bash CN, Maloni H, Frank JA, McFarland HF (1995) Bloodbrain barrier disruption on contrast-enhanced MRI in patients with mild relapsing-remitting multiple sclerosis: relationship to course, gender, and age. Neurology 45: 1122-1126.
98. Takasugi N, Sasaki T, Ebinuma I, Osawa S, Isshiki H, Takeo K, Tomita T, Iwatsubo T (2013) FTY720/fingolimod, a sphingosine analogue, reduces amyloid-beta production in neurons. PLoS ONE 8: e64050.
99. Terai K, Soga T, Takahashi M, Kamohara M, Ohno K, Yatsugi S, Okada M, Yamaguchi T (2003) Edg-8 receptors are preferentially expressed in oligodendrocyte lineage cells of the rat CNS. Neuroscience 116: 1053-1062.
100. Toman RE, Payne SG, Watterson KR, Maceyka M, Lee NH, Milstien S, Bigbee JW, Spiegel S (2004) Differential transactivation of sphingosine-1-phosphate receptors modulates NGFinduced neurite extension. J Cell Biol 166: 381-392.
101. Vajkoczy P, Laschinger M, Engelhardt B (2001) Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J Clin Invest 108: 557-565.
102. van Doorn R, van Horssen J, Verzijl D, Witte M, Ronken E, van Het Hof B, Lakeman K, Dijkstra CD, van Der Valk P, Reijerkerk A et al (2010) Sphingosine 1-phosphate receptor 1 and 3 are upregulated in multiple sclerosis lesions. Glia 58: 1465-1476.
103. van Doorn R, Nijland PG, Dekker N, Witte ME, Lopes-Pinheiro MA, van het Hof B, Kooij G, Reijerkerk A, Dijkstra C, van van der Valk P et al (2012a) Fingolimod attenuates ceramideinduced blood-brain barrier dysfunction in multiple sclerosis by targeting reactive astrocytes. Acta Neuropathol 124: 397-410.
104. van Doorn R, Lopes Pinheiro MA, Kooij G, Lakeman K, van het Hof B, van der Pol SM, Geerts D, van Horssen J, van der Valk P, van der Kam E et al (2012b) Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier. J Neuroinflammation 9: 133.
105. Wacker BK, Perfater JL, Gidday JM (2012) Hypoxic preconditioning induces stroke tolerance in mice via a cascading HIF, sphingosine kinase, and CCL2 signaling pathway. J Neurochem 123: 954-962.
106. Waubant E, Goodkin DE, Gee L, Bacchetti P, Sloan R, Stewart T, Andersson PB, Stabler G, Miller K (1999) Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis. Neurology 53: 1397-1401.
107. Webb M, Tham CS, Lin FF, Lariosa-Willingham K, Yu N, Hale J, Mandala S, Chun J, Rao TS (2004) Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. J Neuroimmunol 153: 108-121.
108. Wei Y, Yemisci M, Kim HH, Yung LM, Shin HK, Hwang SK, Guo S, Qin T, Alsharif N, Brinkmann V et al (2011) Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol 69: 119-129.
109. Wu YP, Mizugishi K, Bektas M, Sandhoff R, Proia RL (2008) Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease. Hum Mol Genet 17: 2257-2264.
110. Wu C, Leong SY, Moore CS, Cui QL, Gris P, Bernier LP, Johnson TA, Seguela P, Kennedy TE, Bar-Or A et al (2013) Dual effects of daily FTY720 on human astrocytes in vitro: relevance for neuroinflammation. J Neuroinflammation 10: 41.
111. Yang J, Noyan-Ashraf MH, Meissner A, Voigtlaender-Bolz J, Kroetsch JT, Foltz W, Jaffray D, Kapoor A, Momen A, Heximer SP et al (2012) Proximal cerebral arteries develop myogenic responsiveness in heart failure via tumor necrosis factor-alpha-dependent activation of sphingosine-1-phosphate signaling. Circulation 126: 196-206.
112. Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (1992) Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 356: 63-66.
113. Young N, Pearl DK, van Brocklyn JR (2009) Sphingosine-1-phosphate regulates glioblastoma cell invasiveness through the urokinase plasminogen activator system and CCN1/Cyr61. Mol Cancer Res 7: 23-32.
114. Young KL, Brandt AU, Petzold A, Reitz LY, Lintze F, Paul F, Martin R, Schippling S (2013) Loss of retinal nerve fibre layer axons indicates white but not grey matter damage in early multiple sclerosis. Eur J Neurol 20: 803-811.
115. Yu N, Lariosa-Willingham KD, Lin FF, Webb M, Rao TS (2004) Characterization of lysophosphatidic acid and sphingosine-1-phosphate-mediated signal transduction in rat cortical oligodendrocytes. Glia 45: 17-27.
116. Zhu D, Wang Y, Singh I, Bell RD, Deane R, Zhong Z, Sagare A, Winkler EA, Zlokovic BV (2010) Protein S controls hypoxic/ischemic blood-brain barrier disruption through the TAM receptor Tyro3 and sphingosine 1-phosphate receptor. Blood 115: 4963-4972.