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FTY720 in CNS injuries: Molecular mechanisms and therapeutic potential.
Brain Research Bulletin ( IF 3.8 ) Pub Date : 2020-08-23 , DOI: 10.1016/j.brainresbull.2020.08.013
Li Zhang 1 , Handong Wang 1
Affiliation  

Central nervous system (CNS) injuries, such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), are important causes of disability and death worldwide. FTY720, a structural sphingosine analog and sphingosine-1-phosphate receptor (S1PR) modulator, is currently used in the treatment of relapsing-remitting multiple sclerosis (RRMS). However, recent in vivo and in vitro studies suggest that FTY720 plays a key role in many neurological diseases, especially in CNS injuries. In addition, FTY720 is under clinical trial for the treatment of acute stroke and ICH. FTY720 could exert anti-apoptosis, anti-inflammation and anti-oxidative stress effects in CNS injuries through different molecules and pathways such as sphingosine-1-phosphate receptor (S1PR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), protein phosphatase 2A (PP2A) and P2 × 7 receptor (P2 × 7R). Thus, FTY720 shows great promise for the treatment of CNS injuries. This review covers a brief introduction about the relationship between FTY270 and CNS injuries, and an updated overview of downstream molecules of FTY720 in CNS injuries.



中文翻译:

中枢神经系统损伤中的 FTY720:分子机制和治疗潜力。

中枢神经系统 (CNS) 损伤,如外伤性脑损伤 (TBI)、蛛网膜下腔出血 (SAH) 和脑内出血 (ICH),是全球致残和死亡的重要原因。FTY720 是一种结构性鞘氨醇类似物和 1-磷酸鞘氨醇受体 (S1PR) 调节剂,目前用于治疗复发缓解型多发性硬化症 (RRMS)。然而,最近的体内体外研究表明 FTY720 在许多神经系统疾病中起着关键作用,尤其是在中枢神经系统损伤中。此外,FTY720 正在临床试验中用于治疗急性中风和 ICH。FTY720可通过1-磷酸鞘氨醇受体(S1PR)、活化B细胞核因子κ-轻链增强子等不同分子和途径在中枢神经系统损伤中发挥抗凋亡、抗炎和抗氧化应激作用。 NF-κB)、磷脂酰肌醇-4,5-二磷酸 3-激酶/蛋白激酶 B (PI3K/AKT)、蛋白磷酸酶 2A (PP2A) 和 P2 × 7 受体 (P2 × 7R)。因此,FTY720 显示出治疗中枢神经系统损伤的巨大希望。本综述简要介绍了 FTY270 与 CNS 损伤之间的关系,以及 FTY720 下游分子在 CNS 损伤中的最新概述。

更新日期:2020-08-29
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