Necroptosis in sepsis: Mechanisms and therapeutic potential
Lu Wang, Yuan Cao, Yiqi Wu, Yun Li, Yang Bai, Qiyuan Zhou, Min Wang, Chengjin Wang, Zhen Gao, Zhirong Qian, Xiangmei Chen, Hongjun Kang
Abstract
Sepsis, a life-threatening condition characterized by systemic inflammatory responses, remains a significant challenge in clinical settings due to its complex pathogenesis and limited therapeutic strategies. Central to this conundrum is the role of cell death mechanisms, particularly necroptosis, in the progression and resolution of sepsis. Necroptosis, a regulated form of necrotic cell death, not only exacerbates inflammation through the release of intracellular contents but also compromises barrier functions, facilitating microbial translocation and systemic spread. While current therapeutic approaches predominantly focus on broad-spectrum antibiotics and supportive care, they often overlook the intricate interplay of cell death pathways and the host immune response. This review aims to shed light on the mechanistic intricacies of necroptosis in sepsis and its potential as a promising therapeutic target. By understanding and modulating necroptosis, we may unlock innovative strategies that address the current shortcomings in sepsis treatment and pave the way for a new era of targeted therapies.