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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
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.
Type: article
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)

Submitter: 川堀 真人

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