坏死性凋亡及其在阿尔茨海默病病理进展中的作用OA

Alzheimer's disease(AD)is a common degenerative disease of the central nervous system,characterized by major pathological features including senile plaques formed by amyloid beta(Aβ)deposition,neurofibrillary tangles mediated by hyperphosphorylated Tau protein,and progressive cognitive dysfunction.Research has found that,in addition to known cell death modalities such as apoptosis,pyroptosis,and ferroptosis,necroptosis,as a precisely regulated form of programmed necrosis,plays a significant role in the process of neuronal loss in AD.Necroptosis is mediated through the RIPK1-RIPK3-MLKL signaling pathway,involving both classical and non-classical routes.It not only directly causes neuronal death but also activates neuroinflammatory responses by releasing damage-associated molecular patterns(DAMPs),thereby forming a vicious cycle that drives the progression of AD.This article systematically reviews the characteristics,signaling pathways,and molecular mechanisms of necroptosis and its role in AD,focusing on its interactions with Tau protein hyperphosphorylation,Aβ deposition,and neuronal death.Integrating clinical and animal model studies,it provides a new perspective for understanding the pathogenesis of AD and reveals the potential of targeting necroptosis as a therapeutic strategy for AD.