ACSL4 in Alzheimer''s disease:Pathogenetic mechanisms and potential therapeutic targetsOA
Iron metabolism plays a vital role in maintaining physiological homeostasis,and its dysregulation is implicated in a range of pathological consequences and illnesses,including Alzheimer''s disease(AD).Prior studies have demonstrated that Tau protein and amyloid precursor protein are involved in iron homeostasis disorder.Ferroptosis,an iron-dependent form of regulated cell death,has emerged as a key contributor to AD pathogenesis and a promising therapeutic target.Acyl-CoA synthetase long-chain family 4(ACSL4)is a lipid metabolizing enzyme that enhances ferroptosis sensitivity by promoting the incorporation of oxidizable polyunsaturated fatty acids into membrane phospholipids.Beyond ferroptosis,ACSL4 also plays crucial roles in neuroinflammation and oxidative stress,which are implicated in AD progression.Therefore,targeting ACSL4 is fantastic and has a lot of promise for treating AD.Nevertheless,the precise mechanisms through which ACSL4 contributes to AD pathology have yet to be fully elucidated.This review reveals a potentially vital role of ACSL4 in AD,focusing on its involvement in ferroptosis,oxidative stress,and neuroinflammation.Additionally,we describe some natural and synthetic compounds targeting ACSL4 with therapeutic potential in AD.Building on the theoretical findings of earlier studies about focused interventions of the ACSL4 path,our evaluation provided a broad basis for the clinical transformation in the treatment of AD strategies.
Yu Guo;Qingqing Jiang;Zhongya Gu;Huan Cao;Chengchao Zuo;Yaqi Huang;Yu Song;Xiang Chen;Furong Wang
Department of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaSchool of Nursing,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Rehabilitation,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,ChinaDepartment of Neurology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China Key Laboratory of Vascular Aging(HUST),Ministry of Education,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China
医药卫生
ACSL4Alzheimer''s diseaseFerroptosisNeuroinflammationOxidative stress
《Genes & Diseases》 2026 (4)
P.238-258,21
funded by the National Key Research and Development Program of Hubei Province(No.2020BCA089)the National Natural Science Foundation of China(No.81974218).
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