Gasdermin D in pyroptosis.
Gasdermin D in pyroptosis.
复制标题
焦亡中的气真皮蛋白D。
DOI：
10.1016/j.apsb.2021.02.006
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Burdette BE;Esparza AN;Zhu H;Wang S
焦亡是炎症细胞死亡的过程。焦亡的主要功能是诱导强烈的炎症反应，保护宿主免受微生物感染。然而，过度的焦亡会导致几种炎症性疾病，包括败血症和自身免疫性疾病。焦亡可为典型或非典型。在微生物感染时，典型途径响应病原体相关分子模式（PAMPs）和损伤相关分子模式（DAMPs），而非典型途径响应革兰氏阴性菌的细胞内脂多糖（LPS）。焦亡的最后一步需要caspase 1在典型途径和caspase 4/5/11（人类caspase 4/5，小鼠caspase 11）在非典型途径中将D275处的gasdermin D （GsdmD后编号）切割成N-和c -末端。GsdmD的n端（GsdmD- n）在裂解后形成跨膜孔，释放IL-1β、IL-18等细胞因子，扰乱离子和水的调控，最终导致强烈炎症和细胞死亡。由于GsdmD是焦亡的效应器，因此已经开发出有前途的GsdmD抑制剂用于炎症性疾病。本文就GsdmD在焦亡和疾病中的作用作一综述。激活的GsdmD作为效应体，通过形成跨膜孔和释放炎性细胞因子触发焦亡。这将导致细胞损伤或引起炎症相关疾病的解决。
Pyroptosis is the process of inflammatory cell death. The primary function of pyroptosis is to induce strong inflammatory responses that defend the host against microbe infection. Excessive pyroptosis, however, leads to several inflammatory diseases, including sepsis and autoimmune disorders. Pyroptosis can be canonical or noncanonical. Upon microbe infection, the canonical pathway responds to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), while the noncanonical pathway responds to intracellular lipopolysaccharides (LPS) of Gram-negative bacteria. The last step of pyroptosis requires the cleavage of gasdermin D (GsdmD) at D275 (numbering after human GSDMD) into N- and C-termini by caspase 1 in the canonical pathway and caspase 4/5/11 (caspase 4/5 in humans, caspase 11 in mice) in the noncanonical pathway. Upon cleavage, the N-terminus of GsdmD (GsdmD-N) forms a transmembrane pore that releases cytokines such as IL-1β and IL-18 and disturbs the regulation of ions and water, eventually resulting in strong inflammation and cell death. Since GsdmD is the effector of pyroptosis, promising inhibitors of GsdmD have been developed for inflammatory diseases. This review will focus on the roles of GsdmD during pyroptosis and in diseases. As the effector, activated GsdmD triggers pyroptosis by forming transmembrane pores and releasing inflammatory cytokines. This will lead to the resolution of cellular insults or cause inflammation-related diseases.
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DOI：
10.1073/pnas.1607769113
发表时间：
2016-07-12
影响因子：
11.1
作者：
Aglietti, Robin A.;Estevez, Alberto;Dueber, Erin C.
通讯作者：
Dueber, Erin C.
影响因子：
12.4
作者：
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影响因子：
14.8
作者：
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通讯作者：
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影响因子：
32.4
作者：
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通讯作者：
Rathinam VAK
影响因子：
30.5
作者：
Choi, Youn Jung;Kim, Stephanie;Jung, Jae U.
通讯作者：
Jung, Jae U.