Progress in study on the final executor of necroptosis MLKL and its inhibitors.
10.11817/j.issn.1672-7347.2023.220411
- Author:
Xuyan LIU
1
;
Hua TU
2
;
Jun PENG
3
Author Information
1. Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078. 217211073@csu.edu.cn.
2. Department of Pharmacy, Fourth Hospital of Changsha, Changsha 410006, China.
3. Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078. junpeng@csu.edu.cn.
- Publication Type:Journal Article
- Keywords:
cancer;
cardiovascular diseases;
mixed lineage kinase domain like protein;
necroptosis;
neurodegenerative diseases
- MeSH:
Protein Kinases/metabolism*;
Necroptosis/physiology*;
Receptor-Interacting Protein Serine-Threonine Kinases;
Signal Transduction;
Pyroptosis;
Apoptosis
- From:
Journal of Central South University(Medical Sciences)
2023;48(2):242-251
- CountryChina
- Language:English
-
Abstract:
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.
