The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
FTY720 modulates human oligodendrocyte progenitor process extension and survival
Abstract
Objective: FTY720, a sphingosine‐1‐phosphate (S1P) receptor agonist that crosses the blood–brain barrier, is a potential immuno‐therapy for multiple sclerosis. Our objective was to assess the effect of FTY720 on process extension, differentiation, and survival of human oligodendrocyte progenitor cells (OPCs), and link the functional effects with S1P receptor expression and signaling. Methods: Functional assays and receptor expression studies were conducted on A2B5+ OPCs derived from the human fetal central nervous system. Cells were treated with physiologically relevant concentrations of the active phosphorylated form of FTY720. S1P receptor/signaling modulators were used to elucidate the basis of the FTY720‐induced functional responses. Results: Short‐term (1 day) FTY720 treatment caused initial process retraction that was reversed by uncoupling S1P3 and 5 from their G protein using suramin, and with a Rho‐kinase inhibitor H1152. Retraction was associated with RhoA‐mediated cytoskeletal signaling and with inhibition of OPC differentiation into more mature phenotypes. Continued FTY720 treatment (2 days) induced process extension and enhanced cell survival associated with increased extracellular signal‐regulated kinases 1 and 2 phosphorylation, mimicked with the S1P1‐specific agonist SEW2871, but not reversed with suramin. Quantitative real‐time polymerase chain reaction showed that FTY720 induced reciprocal and cyclic modulation of S1P1 and S1P5 messenger RNA levels. The observed initial downregulation of S1P5 and subsequently of S1P1 messenger RNA supports functional responses being mediated sequentially by S1P5‐ and later S1P1‐associated signaling. Interpretation: FTY720 induces time‐dependent modulation of S1P receptors on human OPCs with consequent functional responses that are directly relevant for the remyelination process. Ann Neurol 2007
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Cites
Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.-J., Card, D., Keohane, C., et al. (2002) · Science · doi:10.1126/science.1070238 · Cited by 1,690
Oral Fingolimod (FTY720) for Relapsing Multiple Sclerosis
Kappos, L., Antel, J., Comi, G., Montalban, X., O'Connor, P., Polman, C. H., Haas, T., Korn, A. A., Karlsson, G., & Radue, E. W. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052643 · Cited by 1,054
Self-citationWhy does remyelination fail in multiple sclerosis?
Franklin, R. J. M. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn917 · Cited by 837
TLR signaling tailors innate immune responses in human microglia and astrocytes
Jack, C. S., Arbour, N., Manusow, J., Montgrain, V., Blain, M., McCrea, E., Shapiro, A., & Antel, J. P. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.7.4320 · Cited by 734 · cited 1×
“Actin transcript levels were used as endogenous controls for the amount of RNA transcribed, and primers/ probes were designed using the PRIMER express software.(32) All S1P receptor levels were normalized to the actin levels in the corresponding sample.”
MethodNunes, M. C., Roy, N. S., Keyoung, H. M., Goodman, R. R., McKhann, G., Jiang, L., Kang, J., Nedergaard, M., & Goldman, S. A. (2003) · Nature Medicine · doi:10.1038/nm837 · Cited by 656
LINGO-1 negatively regulates myelination by oligodendrocytes
Mi, S., Miller, R. H., Lee, X., Scott, M. L., Shulag-Morskaya, S., Shao, Z., Chang, J., Thill, G., Levesque, M., Zhang, M., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1460 · Cited by 628
Endogenous progenitors remyelinate demyelinated axons in the adult CNS
Gensert, J. M., & Goldman, J. E. (1997) · Neuron · doi:10.1016/s0896-6273(00)80359-1 · Cited by 544
The immunosuppressant FTY720 down‐regulates sphingosine 1‐phosphate G protein‐coupled receptors
Gräler, M. H., & Goetzl, E. J. (2004) · The FASEB Journal · doi:10.1096/fj.03-0910fje · Cited by 539
Brinkmann, V., Cyster, J. G., & Hla, T. (2004) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2004.00476.x · Cited by 478
Le-Niculescu, H., Bonfoco, E., Kasuya, Y., Claret, F.-X., Green, D. R., & Karin, M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.1.751 · Cited by 465
Cited by
A Placebo-Controlled Trial of Oral Fingolimod in Relapsing Multiple Sclerosis
Kappos, L., Radue, E.-W., O'Connor, P., Polman, C., Hohlfeld, R., Calabresi, P., Selmaj, K., Agoropoulou, C., Leyk, M., Zhang-Auberson, L., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0909494 · Cited by 2,644
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., & Burtin, P. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3248 · Cited by 1,273
Kuhlmann, T., Miron, V., Cuo, Q., Wegner, C., Antel, J., & Bruck, W. (2008) · Brain · doi:10.1093/brain/awn096 · Cited by 864
Self-citationMechanism of Action of Oral Fingolimod (FTY720) in Multiple Sclerosis
Chun, J., & Hartung, H.-P. (2010) · Clinical Neuropharmacology · doi:10.1097/wnf.0b013e3181cbf825 · Cited by 796
Brinkmann, V. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00451.x · Cited by 438
Metadata
- Authors
- Miron, V. E., Jung, C. G., Kim, H. J., Kennedy, T. E., Soliven, B., & Antel, J. P.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2007-10-04
- Volume
- 63
- Issue
- 1
- Pages
- 61-71
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2049363669
- Cited by
- 255
- References
- 49
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- closed
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- Miron, V. E., Jung, C. G., Kim, H. J., Kennedy, T. E., Soliven, B., & Antel, J. P. (2008). FTY720 modulates human oligodendrocyte progenitor process extension and survival. Annals of Neurology. https://doi.org/10.1002/ana.21227
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