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gasdermin 家族:脑卒中治疗的有潜力靶点

Gasdermin Family: a Promising Therapeutic Target for Stroke.

机构信息

Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, NO.88 Jiefang Rd, Hangzhou, 310009, China.

Department of Neurosurgery, Taizhou Hospital, Wenzhou Medical University, Linhai, Zhejiang, China.

出版信息

Transl Stroke Res. 2018 Dec;9(6):555-563. doi: 10.1007/s12975-018-0666-3. Epub 2018 Oct 3.

Abstract

Stroke is one of the leading causes of death worldwide and therapies are limited. According to the mechanisms underlying stroke, direct cell demise, destruction of organelles, blood-brain barrier disruption, neuroinflammation are potential therapeutic targets. Gasdermin (GSDM) family is a series of recently discovered proteins, which acts as the executor of pyroptosis and protagonist of membrane pore formation. It can be cleaved by inflammatory caspases that are activated by multi-protein complexes, named as inflammasomes, and divided into two domains. The N-terminal domain interacts with lipid localized in the plasma membrane as well as organelle membrane and perforates them. After the formation of pores, the dysfunctional structures suffer lytic death and their contents are released. In this review, we discuss the biological characteristic of GSDM family and their possible roles in stroke-induced brain injury, and based on the review, we hypothesize the feasibility of using GSDMs as a potential target for stroke treatment.

摘要

中风是全球主要的死亡原因之一,治疗方法有限。根据中风的发病机制,直接细胞死亡、细胞器破坏、血脑屏障破坏、神经炎症是潜在的治疗靶点。Gasdermin (GSDM) 家族是最近发现的一系列蛋白质,作为细胞焦亡的执行者和膜孔形成的主角。它可以被炎性小体激活的炎症半胱天冬酶切割,炎性小体是一种多蛋白复合物,可分为两个结构域。N 端结构域与位于质膜和细胞器膜上的脂质相互作用,并使它们穿孔。形成孔后,功能失调的结构会发生裂解性死亡,其内容物被释放。在这篇综述中,我们讨论了 GSDM 家族的生物学特性及其在中风引起的脑损伤中的可能作用,并基于综述,我们假设将 GSDMs 用作中风治疗的潜在靶点的可行性。

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