程序性细胞坏死:从分子机制到疾病OA

Necroptosis is a cysteinyl aspartate specific proteinase(caspase)-independent form of programmed cell death mediated by death receptors and executed by the mixed lineage kinase domain-like protein(MLKL),which exhibits typical morphological features of necrosis.The core signaling pathway of necroptosis is initiated by the activation of signals such as death receptors.Key steps include the complex formation of receptor-interacting protein kinase 1(RIPK1)and RIPK3,which subsequently recruits and phosphorylates the downstream effector MLKL,ultimately leading to plasma membrane rupture.Activated MLKL undergoes oligomerization and translocates to the plasma membrane,where it disrupts membrane integrity either by di-rect pore formation or indirect regulation of ion channels,resulting in intracellular content leakage and in-flammatory responses.Substantial evidence indicates that dysregulated necroptosis is closely associated with the pathophysiology of various human diseases,including inflammatory disorders,immune-related conditions,degenerative diseases,and cancer.This review aims to summarize the core molecular mechanisms and sig-naling networks of necroptosis,as well as its roles in related diseases,thereby providing a theoretical founda-tion for developing therapeutic strategies targeting this pathway.