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FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment
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| Title: | FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment |
| Authors: | Wang, Zifeng Browse this author | | Kawabori, Masahiro Browse this author →KAKEN DB | | Houkin, Kiyohiro Browse this author →KAKEN DB |
| Keywords: | FTY720 | | fingolimod | | stroke | | sphingosinc-l-phosphatc | | inflammation | | sphingosinc kinase |
| Issue Date: | 4-Jun-2020 |
| Publisher: | Bentham Science Publishers |
| Journal Title: | Current medicinal chemistry |
| Volume: | 27 |
| Issue: | 18 |
| Start Page: | 2979 |
| End Page: | 2993 |
| Publisher DOI: | 10.2174/0929867326666190308133732 |
| Abstract: | FTY720 (Fingolimod) is a known sphingosine-1-phosphate (SIP) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. FTY720 is mainly associated with unique functional "antagonist" and "agonist" mechanisms. The functional antagonistic mechanism is mediated by the transient down-regulation and degradation of SW receptors on lymphocytes, which prevents lymphocytes from entering the blood stream from the lymph node. This subsequently results in the development of lymphopenia and reduces lymphocytic inflammation. Functional agonistic mechanisms are executed through Si P receptors expressed on the surface of various cells including neurons, astrocytes, microglia, and blood vessel endothelial cells. These functions might play important roles in regulating anti-apoptotic systems, modulating brain immune and phagocytic activities, preserving the Blood-Brain-Barrier (BBB), and the proliferation of neural precursor cells. Recently, FTY720 have shown receptor-independent effects, including intracellular target bindings and epigenetic modulations. Many researchers have recognized the positive effects of FTY720 and launched basic and clinical experiments to test the use of this agent against stroke. Although the mechanism of FTY720 has not been fully elucidated, its efficacy against cerebral stroke is becoming clear, not only in animal models, but also in ischemic stroke patients through clinical trials. In this article, we review the data obtained from laboratory findings and preliminary clinical trials using FTY720 for stroke treatment. |
| Rights: | https://creativecommons.org/licenses/by/4.0/legalcode |
| Type: | article |
| URI: | http://hdl.handle.net/2115/78884 |
| Appears in Collections: | 北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 川堀 真人
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