| First Author | Takasugi N | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 5 | Pages | e64050 |
| PubMed ID | 23667698 | Mgi Jnum | J:200531 |
| Mgi Id | MGI:5508825 | Doi | 10.1371/journal.pone.0064050 |
| Citation | Takasugi N, et al. (2013) FTY720/fingolimod, a sphingosine analogue, reduces amyloid-beta production in neurons. PLoS One 8(5):e64050 |
| abstractText | Sphingosine-1-phosphate (S1P) is a pluripotent lipophilic mediator working as a ligand for G-protein coupled S1P receptors (S1PR), which is currently highlighted as a therapeutic target for autoimmune diseases including relapsing forms of multiple sclerosis. Sphingosine related compounds, FTY720 and KRP203 known as S1PR modulators, are phosphorylated by sphingosine kinase 2 (SphK2) to yield the active metabolites FTY720-P and KRP203-P, which work as functional antagonists for S1PRs. Here we report that FTY720 and KRP203 decreased production of Amyloid-beta peptide (Abeta), a pathogenic proteins causative for Alzheimer disease (AD), in cultured neuronal cells. Pharmacological analyses suggested that the mechanism of FTY720-mediated Abeta decrease in cells was independent of known downstream signaling pathways of S1PRs. Unexpectedly, 6-days treatment of APP transgenic mice with FTY720 resulted in a decrease in Abeta40, but an increase in Abeta42 levels in brains. These results suggest that S1PR modulators are novel type of regulators for Abeta metabolisms that are active in vitro and in vivo. |
