Mechanism of action and progress of mitophagy,ferroptosis,cuproptosis,and disulfidptosis in Alzheimer's disease
- VernacularTitle:线粒体自噬、铁死亡、铜死亡和双硫死亡在阿尔茨海默病中的作用机制及进展
- Author:
Dandan LIU
1
;
Hewei QIN
Author Information
- Keywords: Alzheimer's disease; procedural death; mitophagy; ferroptosis; cuproptosis; disulfidptosis; apoptosis; necroptosis; pyroptosis
- From: Chinese Journal of Tissue Engineering Research 2025;29(19):4132-4144
- CountryChina
- Language:Chinese
- Abstract: BACKGROUND:In recent years,with the in-depth study of programmed cell death,new models of programmed cell death(mitophagy,ferroptosis,cuproptosis,and disulfidptosis)involved in Alzheimer's disease injury are gradually emerging and have large research space in the future. OBJECTIVE:To review the molecular mechanism of novel programmed cell death mode(mitophagy,ferroptosis,cuproptosis,and disulfidptosis),the crosstalk mechanism of novel cell death mode,and clinical transformation in Alzheimer's disease,aiming to provide a new perspective for exploring the mechanism of action and drug targets in Alzheimer's disease. METHODS:The first author used the computer to search the literature published between 1991 and 2024.101 articles were finally included according to the inclusion criteria. RESULTS AND CONCLUSION:(1)Programmed cell death is a necessary regulatory pathway to maintain normal cell renewal and homeostasis.Among them,new types of programmed cell death such as mitophagy,ferroptosis,cuproptosis,and disulfidptosis are hot research fields in life science.(2)Mitophagy can clear damaged mitochondria in Alzheimer's disease neurons,reduce intracellular reactive oxygen species,restore the energy metabolism and signal transduction of neurons in Alzheimer's disease,and play a crucial role in regulating the health and function of neurons.(3)Studies on ferroptosis in Alzheimer's disease have attracted much attention.It can regulate Alzheimer's disease through various ways such as cystine/glutamate,iron metabolism,and polyunsaturated fatty acids,thus affecting Aβ deposition and Tau protein phosphorylation.Recent studies have shown that natural polyphenols,Suanzoren decoction,poria acid,and vitamin E can resist ferroptosis in Alzheimer's disease.(4)Cuproptosis is a new and unique form of cell death involving copper dependence,accumulation of fatty acylated proteins,and reduction of iron-sulfur tufting proteins.Excessive copper exposure may directly interact with Aβ plaques and amyloid precursor proteins,exacerbating cognitive impairment in Alzheimer's disease.Currently,the research field of cuproptosis is emerging,and the mechanism of action has not been fully clarified.(5)Disulfidptosis,as an emerging form of programmed cell death,is caused by disulfide stress due to excessive cystine accumulation and glucose starvation,resulting in damage to the actin skeleton associated with Alzheimer's disease.(6)Various patterns of programmed cell death have a tandem mechanism in the pathogenesis of Alzheimer's disease,forming an interaction network of various programmed cell death with autophagy as the core,providing great potential for multi-level and multi-target regulation of Alzheimer's disease.The crosstalk network mechanism between autophagy,necroptosis,and pyroptosis/ferroptosis co-regulates Alzheimer's disease.(7)Cuproptosis and disulfidptosis,as a new mode of programmed death,have not been reported deeply enough in Alzheimer's disease,and further research and continuous attentions are still needed in the future.(8)Since most studies on mitophagy,ferroptosis,cuproptosis,and disulfidptosis are based on basic experiments or biogenic analysis,there is a lack of large-scale and long-term clinical research validation.Further in-depth studies are needed in the future to provide new ideas and effective strategies for the treatment of Alzheimer's disease.
