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鞘脂途径在中风中的关键作用:当前应用及潜在治疗靶点综述

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

作者信息

Sun Na, Keep Richard F, Hua Ya, Xi Guohua

机构信息

Department of Neurosurgery, University of Michigan, 5018 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.

Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China.

出版信息

Transl Stroke Res. 2016 Oct;7(5):420-38. doi: 10.1007/s12975-016-0477-3. Epub 2016 Jun 24.

Abstract

Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

摘要

鞘脂是一系列源自细胞膜的脂质,它们作为信号分子,在细胞死亡与存活、增殖、识别及迁移过程中发挥关键作用。1-磷酸鞘氨醇作为一种关键信号分子,可调节淋巴细胞运输、神经胶质细胞激活、血管收缩、内皮屏障功能以及神经元死亡途径,而这些在众多神经疾病中起着关键作用。中风是全球第二大致死原因,目前仍迫切需要有效的治疗方法,包括缺血性中风、出血性中风以及中风后的修复。值得注意的是,中风后鞘脂活性会发生变化,且与中风预后相关,这促使人们努力证实鞘脂途径是否可能成为中风的新型治疗靶点。本文综述了鞘脂代谢途径、该途径与中风的联系,以及通过调控该途径来减轻中风所致脑损伤的治疗干预措施。

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