δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities
作者机构：Department of NeurologyRenmin Hospital of Wuhan UniversityWuhan 430060People’s Republic of China Department of Pathology and Laboratory MedicineEmory University School of MedicineAtlantaGA 30322USA
出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)
年 卷 期：2020年第9卷第1期
页 面：1-9页
核心收录：
学科分类：0710[理学-生物学] 0402[教育学-心理学(可授教育学、理学学位）] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 1010[医学-医学技术（可授医学、理学学位）] 100204[医学-神经病学] 10[医学] 1009[医学-特种医学]
基 金：This work is supported by grants from the National Institute of Health(RF1,AG051538,RO1,NS105982)to K.Ye grants from the National Natural Science Foundation of China(No.81822016,81771382,and 81571249)to Z.Zhang.
主 题：AEP Alzheimer’s disease Parkinson’s disease C/EBPβ TrkB TDP-43
摘 要：Mammalian asparagine endopeptidase(AEP)is a cysteine protease that cleaves its protein substrates on the Cterminal side of asparagine residues.Converging lines of evidence indicate that AEP may be involved in the pathogenesis of several neurological diseases,including Alzheimer’s disease,Parkinson’s disease,and frontotemporal dementia.AEP is activated in the aging brain,cleaves amyloid precursor protein(APP)and promotes the production of amyloid-β(Aβ).We renamed AEP to δ-secretase to emphasize its role in APP fragmentation and Aβ production.AEP also cleaves other substrates,such as tau,α-synuclein,SET,and TAR DNA-binding protein 43,generating neurotoxic fragments and disturbing their physiological functions.The activity of δ-secretase is tightly regulated at both the transcriptional and posttranslational levels.Here,we review the recent advances in the role of δ-secretase in neurodegenerative diseases,with a focus on its biochemical properties and the transcriptional and posttranslational regulation of its activity,and discuss the clinical implications of δ-secretase as a diagnostic biomarker and therapeutic target for neurodegenerative diseases.
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