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细胞焦亡的分子机制

Molecular Mechanisms of Pyroptosis.

作者信息

Anderson Marisa J, den Hartigh Andreas B, Fink Susan L

机构信息

Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA.

出版信息

Methods Mol Biol. 2023;2641:1-16. doi: 10.1007/978-1-0716-3040-2_1.

Abstract

Pyroptosis is a regulated form of cell death that leads to inflammation and plays a role in many different diseases. Pyroptosis was initially defined by the dependence on caspase-1, a protease which is activated by innate immune signaling complexes called inflammasomes. Caspase-1 cleaves the protein gasdermin D, releasing the N-terminal pore-forming domain, which inserts into the plasma membrane. Recent studies have revealed that other gasdermin family members form plasma membrane pores, leading to lytic cell death, and the definition of pyroptosis was revised to gasdermin-dependent cell death. In this review, we discuss how the use of the term pyroptosis has changed over time, as well as currently understood molecular mechanisms leading to pyroptosis and functional consequences of this form of regulated cell death.

摘要

细胞焦亡是一种受调控的细胞死亡形式,可导致炎症反应,并在多种不同疾病中发挥作用。细胞焦亡最初被定义为依赖半胱天冬酶-1,这是一种由称为炎性小体的先天免疫信号复合物激活的蛋白酶。半胱天冬酶-1切割gasdermin D蛋白,释放出N端成孔结构域,该结构域插入质膜。最近的研究表明,其他gasdermin家族成员也能形成质膜孔,导致细胞溶解性死亡,因此细胞焦亡的定义被修订为gasdermin依赖性细胞死亡。在这篇综述中,我们讨论了细胞焦亡这一术语的使用是如何随时间变化的,以及目前所了解的导致细胞焦亡的分子机制和这种受调控的细胞死亡形式的功能后果。

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