Potential role and therapeutic implications of glutathione peroxidase 4 in the treatment of Alzheimer's disease
Yanxin Shen
Guimei Zhang
Chunxiao Wei
Panpan Zhao
Yongchun Wang
Mingxi Li
Li Sun
Department of Neurology and Neuroscience Center,The First Hospital of Jilin University,Jilin University,Changchun,Jilin Province,China;Cognitive Impairment Center,Department of Neurology,The First Hospital of Jilin University,Jilin University,Changchun,Jilin Province,China
摘要：Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis.Despite extensive research,a cure for Alzheimer's disease has not yet been found.Oxidative stress mediates excessive oxidative responses,and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted.As a member of the selenium-containing antioxidant enzyme family,glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis.With the discovery of ferroptosis,the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases,including Alzheimer's disease,has received widespread attention.Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain,resulting in oxidative stress,inflammation,ferroptosis,and apoptosis,which are closely associated with pathological damage in Alzheimer's disease.Several therapeutic approaches,such as small molecule drugs,natural plant products,and non-pharmacological treatments,ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity.Therefore,glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease.This review provides an overview of the gene structure,biological functions,and regulatory mechanisms of glutathione peroxidase 4,a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease,and a summary of the advances in small-molecule drugs,natural plant products,and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease.Most prior studies on this subject used animal models,and relevant clinical studies are lacking.Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
机标关键词：alzheimerrolediseaseglutathioneimplicationsperoxidasepotentialtherapeutic
论文发表日期：2025-03-27
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：19( 613-631 )
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