Yazdi Azadeh, Ghasemi-Kasman Maryam, Javan Mohammad
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
J Neurosci Res. 2020 Mar;98(3):524-536. doi: 10.1002/jnr.24509. Epub 2019 Aug 5.
Fingolimod (FTY720) is a sphingosine 1-phosphate (S1P) receptor analog, which has been approved as an oral immunomodulator for treating relapsing-remitting multiple sclerosis. This drug prevents lymphocyte egression from lymph nodes and reduces the infiltration of inflammatory mediators into the central nervous system. Based on its lipophilic nature, FTY720 passes through the blood-brain barrier and can directly affect neural cells. A notably different subtype of S1P receptors expresses in neural cells, which suggests FTY720 is a drug capable of affecting neural cells. Oligodendrocytes (OLs) are considered as the primary target cells in MS. Remyelination is a process including the proliferation of neural progenitors and oligodendrocyte precursor cells, their migration to the lesion site and their differentiation to mature oligodendrocytes. Experimental and clinical studies have described the impact of FTY720 on endogenous remyelination elements. In this review, we will explain the current clinical and experimental evidence that exists on the effects of FTY720 on remyelination and the underlying mechanisms.
芬戈莫德(FTY720)是一种1-磷酸鞘氨醇(S1P)受体类似物,已被批准作为口服免疫调节剂用于治疗复发缓解型多发性硬化症。该药物可阻止淋巴细胞从淋巴结逸出,并减少炎症介质向中枢神经系统的浸润。基于其亲脂性,FTY720可穿过血脑屏障并直接影响神经细胞。神经细胞中表达一种明显不同的S1P受体亚型,这表明FTY720是一种能够影响神经细胞的药物。少突胶质细胞(OLs)被认为是多发性硬化症的主要靶细胞。髓鞘再生是一个包括神经祖细胞和少突胶质前体细胞增殖、它们迁移到损伤部位并分化为成熟少突胶质细胞的过程。实验和临床研究已经描述了FTY720对内源性髓鞘再生成分的影响。在这篇综述中,我们将解释目前关于FTY720对髓鞘再生的影响及其潜在机制的临床和实验证据。