Walter Silke, Fassbender Klaus
Department of Neurology, University of the Saarland, Homburg, Germany.
Cell Physiol Biochem. 2010;26(1):49-56. doi: 10.1159/000315105. Epub 2010 May 18.
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system, mainly affecting young adults. Current therapeutic approaches focus on the suppression of the immune system and on blockade of T cell blood-brain barrier transmigration into the brain parenchyma. Recently, sphingolipids that have been linked to MS pathophysiology, i.e., Sphingosine-1-phosphate (S1P), intracellularly produced lysophospholipids, can be recognized by receptors located on T and B cells. The recent demonstration that S1P is able to direct lymphocyte trafficking between blood and lymphoid system has been translated into therapeutic application: A S1P analogue, FTY720, is currently under clinical investigation in MS. Further cell membrane lipids that are involved in cell proliferation, signalling cascades and apoptosis might be of relevance in MS pathophysiology and, thus, await further investigation. This review focuses on the current knowledge on the role of sphingolipids in MS and discusses their potential therapeutical implications.
多发性硬化症(MS)是一种中枢神经系统的慢性炎症性疾病,主要影响年轻人。目前的治疗方法侧重于抑制免疫系统以及阻断T细胞穿越血脑屏障进入脑实质。最近,已发现与MS病理生理学相关的鞘脂,即鞘氨醇-1-磷酸(S1P),细胞内产生的溶血磷脂,可被位于T细胞和B细胞上的受体识别。最近有证据表明S1P能够指导淋巴细胞在血液和淋巴系统之间的运输,这已转化为治疗应用:一种S1P类似物FTY720目前正在MS的临床研究中。其他参与细胞增殖、信号级联反应和细胞凋亡的细胞膜脂质可能与MS病理生理学相关,因此有待进一步研究。本综述重点介绍了目前关于鞘脂在MS中作用的知识,并讨论了它们潜在的治疗意义。