δ-secretase in neurodegenerative diseases: mechanisms, regulators and therapeutic opportunities  

作　　者：Zhentao Zhang Ye Tian Keqiang Ye 

机构地区：[1]Department of Neurology,Renmin Hospital of Wuhan University,Wuhan 430060,People’s Republic of China [2]Department of Pathology and Laboratory Medicine,Emory University School of Medicine,Atlanta,GA 30322,USA

出　　处：《Translational Neurodegeneration》2020年第1期1-9,共9页转化神经变性病（英文）

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.

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.

关 键 词：AEP Alzheimer’s DISEASE Parkinson’s DISEASE C/EBPΒ TrkB TDP-43 

分 类 号：R741[医药卫生—神经病学与精神病学]