Neuronal regulated cell death in aging-related neurodegenerative diseases:key pathways and therapeutic potentials  

作　　者：Run Song Shiyi Yin Jiannan Wu Junqiang Yan 

机构地区：[1]Department of Neurology,The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Luoyang,Henan Province,China [2]Neuromolecular Biology Laboratory,The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Luoyang,Henan Province,China

出　　处：《Neural Regeneration Research》2025年第8期2245-2263,共19页中国神经再生研究（英文版）

基　　金：supported by the Key Projects of Medical Science and Technology of Henan Province,No.SBGJ202002099(to JY)。

摘　　要：Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and death.However,excessive activation of regulated cell death may lead to the progression of aging-related diseases.This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases.Notably,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases.These forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein aggregation.The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and disulfidptosis.For instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis sensitivity.Additionally,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to disulfidptosis.These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms.In conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.

关 键 词：apoptosis autophagy cuproptosis disulfidptosis ferroptosis NECROPTOSIS neurodegenerative disease neurological aging diseases PANoptosis PYROPTOSIS 

分 类 号：R741[医药卫生—神经病学与精神病学]