FTY720/Fingolimod, a Sphingosine Analogue, Reduces Amyloid-β Production in Neurons

PLoS ONE

Volumn 8, Issue 5, 2013, Pages

  Takasugi, Nobumasa ^a,b,c   Sasaki, Tomoki ^a   Ebinuma, Ihori ^a   Osawa, Satoko ^a   Isshiki, Hayato ^a,b   Takeo, Koji ^a   Tomita, Taisuke ^a   Iwatsubo, Takeshi ^a,b  

^a UNIVERSITY OF TOKYO   (Japan)

^b UNIVERSITY OF TOKYO   (Japan)

^c JUNTENDO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID BETA PROTEIN; BETA SECRETASE 1; FINGOLIMOD; SPHINGOSINE 1 PHOSPHATE;

ALZHEIMER DISEASE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG MECHANISM; FEMALE; MOUSE; NERVE CELL; NERVE CELL CULTURE; NONHUMAN; PROTEIN INTERACTION; PROTEIN METABOLISM; PROTEIN SYNTHESIS INHIBITION; PROTEIN SYNTHESIS REGULATION; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; UPREGULATION;

AMYLOID BETA-PEPTIDES; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; HUMANS; MICE; MICE, INBRED BALB C; NEURONS; PHOSPHOTRANSFERASES (ALCOHOL GROUP ACCEPTOR); PROPYLENE GLYCOLS; SIGNAL TRANSDUCTION; SPHINGOSINE; SULFHYDRYL COMPOUNDS;

EID: 84877113548     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0064050     Document Type: Article

References (52)

1. Haughey NJ, Bandaru VV, Bae M, Mattson MP, (2010) Roles for dysfunctional sphingolipid metabolism in Alzheimer's disease neuropathogenesis. Biochimica et biophysica acta 1801: 878-886.
2. Cutler RG, Kelly J, Storie K, Pedersen WA, Tammara A, et al. (2004) Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America 101: 2070-2075.
3. Han X, D MH, McKeel DW Jr, Kelley J, Morris JC, (2002) Substantial sulfatide deficiency and ceramide elevation in very early Alzheimer's disease: potential role in disease pathogenesis. Journal of neurochemistry 82: 809-818.
4. He X, Huang Y, Li B, Gong CX, Schuchman EH, (2010) Deregulation of sphingolipid metabolism in Alzheimer's disease. Neurobiology of aging 31: 398-408.
5. Grimm MO, Rothhaar TL, Hartmann T, (2012) The role of APP proteolytic processing in lipid metabolism. Experimental brain research Experimentelle Hirnforschung Experimentation cerebrale 217: 365-375.
6. Tomita T, (2009) Secretase inhibitors and modulators for Alzheimer's disease treatment. Expert review of neurotherapeutics 9: 661-679.
7. De Strooper B, Vassar R, Golde T, (2010) The secretases: enzymes with therapeutic potential in Alzheimer disease. Nature reviews Neurology 6: 99-107.
8. Vassar R, Kovacs DM, Yan R, Wong PC, (2009) The beta-secretase enzyme BACE in health and Alzheimer's disease: regulation, cell biology, function, and therapeutic potential. The Journal of neuroscience: the official journal of the Society for Neuroscience 29: 12787-12794.
9. Takasugi N, Tomita T, Hayashi I, Tsuruoka M, Niimura M, et al. (2003) The role of presenilin cofactors in the gamma-secretase complex. Nature 422: 438-441.
10. Vetrivel KS, Thinakaran G, (2010) Membrane rafts in Alzheimer's disease beta-amyloid production. Biochimica et biophysica acta 1801: 860-867.
11. Kalvodova L, Kahya N, Schwille P, Ehehalt R, Verkade P, et al. (2005) Lipids as modulators of proteolytic activity of BACE: involvement of cholesterol, glycosphingolipids, and anionic phospholipids in vitro. The Journal of biological chemistry 280: 36815-36823.
12. Osenkowski P, Ye W, Wang R, Wolfe MS, Selkoe DJ, (2008) Direct and potent regulation of gamma-secretase by its lipid microenvironment. The Journal of biological chemistry 283: 22529-22540.
13. Holmes O, Paturi S, Ye W, Wolfe MS, Selkoe DJ, (2012) Effects of membrane lipids on the activity and processivity of purified gamma-secretase. Biochemistry 51: 3565-3575.
14. Brinkmann V, Billich A, Baumruker T, Heining P, Schmouder R, et al. (2010) Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat Rev Drug Discov 9: 883-897.
15. Aktas O, Kury P, Kieseier B, Hartung HP, (2010) Fingolimod is a potential novel therapy for multiple sclerosis. Nat Rev Neurol 6: 373-382.
16. Zemann B, Kinzel B, Muller M, Reuschel R, Mechtcheriakova D, et al. (2006) Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Blood 107: 1454-1458.
17. Don AS, Martinez-Lamenca C, Webb WR, Proia RL, Roberts E, et al. (2007) Essential requirement for sphingosine kinase 2 in a sphingolipid apoptosis pathway activated by FTY720 analogues. J Biol Chem 282: 15833-15842.
18. Hogenauer K, Billich A, Pally C, Streiff M, Wagner T, et al. (2008) Phosphorylation by sphingosine kinase 2 is essential for in vivo potency of FTY720 analogues. ChemMedChem 3: 1027-1029.
19. Foster CA, Howard LM, Schweitzer A, Persohn E, Hiestand PC, et al. (2007) Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther 323: 469-475.
20. Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, et al. (2011) FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proceedings of the National Academy of Sciences of the United States of America 108: 751-756.
21. Fujino M, Funeshima N, Kitazawa Y, Kimura H, Amemiya H, et al. (2003) Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. The Journal of pharmacology and experimental therapeutics 305: 70-77.
22. Takasugi N, Sasaki T, Suzuki K, Osawa S, Isshiki H, et al. (2011) BACE1 Activity Is Modulated by Cell-Associated Sphingosine-1-Phosphate. The Journal of neuroscience: the official journal of the Society for Neuroscience 31: 6850-6857.
23. Kaneko T, Murakami T, Kawana H, Takahashi M, Yasue T, et al. (2006) Sphingosine-1-phosphate receptor agonists suppress concanavalin A-induced hepatic injury in mice. Biochemical and biophysical research communications 345: 85-92.
24. Kan T, Tominari Y, Morohashi Y, Natsugari H, Tomita T, et al. (2003) Solid-phase synthesis of photoaffinity probes: highly efficient incorporation of biotin-tag and cross-linking groups. Chemical communications: 2244-2245.
25. Tomita T, Takikawa R, Koyama A, Morohashi Y, Takasugi N, et al. (1999) C terminus of presenilin is required for overproduction of amyloidogenic Abeta42 through stabilization and endoproteolysis of presenilin. The Journal of neuroscience: the official journal of the Society for Neuroscience 19: 10627-10634.
26. Tomita T, Maruyama K, Saido TC, Kume H, Shinozaki K, et al. (1997) The presenilin 2 mutation (N141I) linked to familial Alzheimer disease (Volga German families) increases the secretion of amyloid beta protein ending at the 42nd (or 43rd) residue. Proceedings of the National Academy of Sciences of the United States of America 94: 2025-2030.
27. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, et al. (1994) Visualization of A beta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13: 45-53.
28. Qi-Takahara Y, Morishima-Kawashima M, Tanimura Y, Dolios G, Hirotani N, et al. (2005) Longer forms of amyloid beta protein: implications for the mechanism of intramembrane cleavage by gamma-secretase. The Journal of neuroscience: the official journal of the Society for Neuroscience 25: 436-445.
29. Merhi A, Andre B, (2012) Internal amino acids promote Gap1 permease ubiquitylation via TORC1/Npr1/14-3-3-dependent control of the Bul arrestin-like adaptors. Mol Cell Biol 32: 4510-4522.
30. Kopan R, Schroeter EH, Weintraub H, Nye JS, (1996) Signal transduction by activated mNotch: importance of proteolytic processing and its regulation by the extracellular domain. Proceedings of the National Academy of Sciences of the United States of America 93: 1683-1688.
31. Iwata H, Tomita T, Maruyama K, Iwatsubo T, (2001) Subcellular compartment and molecular subdomain of beta-amyloid precursor protein relevant to the Abeta 42-promoting effects of Alzheimer mutant presenilin 2. The Journal of biological chemistry 276: 21678-21685.
32. Imamura Y, Watanabe N, Umezawa N, Iwatsubo T, Kato N, et al. (2009) Inhibition of gamma-secretase activity by helical beta-peptide foldamers. Journal of the American Chemical Society 131: 7353-7359.
33. Becuwe M, Herrador A, Haguenauer-Tsapis R, Vincent O, Leon S, (2012) Ubiquitin-mediated regulation of endocytosis by proteins of the arrestin family. Biochem Res Int 2012: 242764.
34. Fukumoto H, Tomita T, Matsunaga H, Ishibashi Y, Saido TC, et al. (1999) Primary cultures of neuronal and non-neuronal rat brain cells secrete similar proportions of amyloid beta peptides ending at A beta40 and A beta42. Neuroreport 10: 2965-2969.
35. Suzuki K, Hayashi Y, Nakahara S, Kumazaki H, Prox J, et al. (2012) Activity-dependent proteolytic cleavage of neuroligin-1. Neuron 76: 410-422.
36. Karlstrom H, Bergman A, Lendahl U, Naslund J, Lundkvist J, (2002) A sensitive and quantitative assay for measuring cleavage of presenilin substrates. The Journal of biological chemistry 277: 6763-6766.
37. Yamada K, Yabuki C, Seubert P, Schenk D, Hori Y, et al. (2009) Abeta immunotherapy: intracerebral sequestration of Abeta by an anti-Abeta monoclonal antibody 266 with high affinity to soluble Abeta. The Journal of neuroscience: the official journal of the Society for Neuroscience 29: 11393-11398.
38. Takabe K, Paugh SW, Milstien S, Spiegel S, (2008) "Inside-out" signaling of sphingosine-1-phosphate: therapeutic targets. Pharmacol Rev 60: 181-195.
39. Lee MJ, Evans M, Hla T, (1996) The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. The Journal of biological chemistry 271: 11272-11279.
40. Mullershausen F, Craveiro LM, Shin Y, Cortes-Cros M, Bassilana F, et al. (2007) Phosphorylated FTY720 promotes astrocyte migration through sphingosine-1-phosphate receptors. Journal of neurochemistry 102: 1151-1161.
41. Wei SH, Rosen H, Matheu MP, Sanna MG, Wang SK, et al. (2005) Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nature immunology 6: 1228-1235.
42. Miron VE, Jung CG, Kim HJ, Kennedy TE, Soliven B, et al. (2008) FTY720 modulates human oligodendrocyte progenitor process extension and survival. Ann Neurol 63: 61-71.
43. Ni Y, Zhao X, Bao G, Zou L, Teng L, et al. (2006) Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med 12: 1390-1396.
44. Tanaka S, Ishii K, Kasai K, Yoon SO, Saeki Y, (2007) Neural expression of G protein-coupled receptors GPR3, GPR6, and GPR12 up-regulates cyclic AMP levels and promotes neurite outgrowth. J Biol Chem 282: 10506-10515.
45. Thathiah A, Spittaels K, Hoffmann M, Staes M, Cohen A, et al. (2009) The orphan G protein-coupled receptor 3 modulates amyloid-beta peptide generation in neurons. Science 323: 946-951.
46. Liu X, Zhao X, Zeng X, Bossers K, Swaab DF, et al. (2012) beta-Arrestin1 regulates gamma-secretase complex assembly and modulates amyloid-beta pathology. Cell Res.
47. Thathiah A, Horre K, Snellinx A, Vandewyer E, Huang Y, et al. (2012) beta-arrestin 2 regulates Abeta generation and gamma-secretase activity in Alzheimer's disease. Nat Med.
48. Lieven CJ, Ribich JD, Crowe ME, Levin LA, (2012) Redox proteomic identification of visual arrestin dimerization in photoreceptor degeneration after photic injury. Invest Ophthalmol Vis Sci 53: 3990-3998.
49. Osawa S, Funamoto S, Nobuhara M, Wada-Kakuda S, Shimojo M, et al. (2008) Phosphoinositides suppress gamma-secretase in both the detergent-soluble and-insoluble states. J Biol Chem 283: 19283-19292.
50. Gomez-Raja J, Davis DA, (2012) The beta-arrestin-like protein Rim8 is hyperphosphorylated and complexes with Rim21 and Rim101 to promote adaptation to neutral-alkaline pH. Eukaryot Cell 11: 683-693.
51. Shichita T, Sugiyama Y, Ooboshi H, Sugimori H, Nakagawa R, et al. (2009) Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nature medicine 15: 946-950.
52. Kaneider NC, Lindner J, Feistritzer C, Sturn DH, Mosheimer BA, et al. (2004) The immune modulator FTY720 targets sphingosine-kinase-dependent migration of human monocytes in response to amyloid beta-protein and its precursor. FASEB J 18: 1309-1311.