关于坏死样细胞死亡的最终执行者球形蛋白 MLKL 及其抑制剂的研究取得进展。
Progress in study on the final executor of necroptosis MLKL and its inhibitors.
发表日期:2023 Feb 28
作者:
Xuyan Liu, Hua Tu, Jun Peng
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
坏死样细胞死亡(necroptosis)是一种调控性细胞死亡过程,涉及受体相互作用蛋白激酶(RIPK)1/RIPK3/混合谱系激酶结构域相关蛋白(MLKL)信号通路。其中,MLKL是坏死样细胞死亡的最终执行体。RIPK1/RIPK3/MLKL坏死体的形成引发MLKL的磷酸化,激活后的MLKL穿过膜双分子层形成膜孔,破坏细胞膜完整性,导致细胞死亡。除参与坏死样细胞死亡外,MLKL还与其他细胞死亡方式息息相关,如NETosis、pyroptosis和自噬。因此,MLKL参与多种疾病异常细胞死亡通路的病理过程(如心血管疾病、神经退行性疾病和癌症),可能成为多种疾病治疗靶点。了解MLKL在不同细胞死亡中的作用,可以为寻找各种MLKL相关的疾病靶点奠定基础,同时指导MLKL抑制剂的开发和应用。
Necroptosis is one of the regulated cell death, which involves receptor interacting protein kinase (RIPK) 1/RIPK3/mixed lineage kinase domain like protein (MLKL) signaling pathway. Among them, MLKL is the final execution of necroptosis. The formation of RIPK1/RIPK3/MLKL necrosome induces the phosphorylated MLKL, and the activated MLKL penetrates into the membrane bilayer to form membrane pores, which damages the integrity of the membrane and leads to cell death. In addition to participating in necroptosis, MLKL is also closely related to other cell death, such as NETosis, pyroptosis, and autophagy. Therefore, MLKL is involved in the pathological processes of various diseases related to abnormal cell death pathways (such as cardiovascular diseases, neurodegenerative diseases and cancer), and may be a therapeutic target of multiple diseases. Understanding the role of MLKL in different cell death can lay a foundation for seeking various MLKL-related disease targets, and also guide the development and application of MLKL inhibitors.