ApoE4 activates C/EBPβ/δ-secretase with 27-hydroxycholesterol, driving the pathogenesis of Alzheimer’s disease

Zhi-Hao Wang,Yiyuan Xia,Pai Liu, Xia Liu,Laura Edgington-Mitchell,Kecheng Lei,Shan Ping Yu,Xiao-Chuan Wang,Keqiang Ye

Progress in Neurobiology（2021）

Cited 32|Views2

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Abstract

•ApoE4 and 27−OHC co-activate C/EBPβ/δ-secretase signaling in neurons, which is mediated by Aβ and inflammatory cytokines.•ApoE4 and 27−OHC mediate lysosomal δ-secretase leakage, activation, secretion and endocytosis.•27−OHC triggers AD pathologies and cognitive deficits in ApoE4-TR mice via activating C/EBPβ/δ-secretase pathway.

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Key words

24−OHC,27−OHC,δ-secretase, AEP,Aβ,AAV,AD,AFU,ApoE,ApoE3 or ApoE4-TR mice,APP,BACE1,BBB,C/EBPβ,c-Fos,DEA,DLK,CSF,EEA1,ELISA,EM,ERK,FA,fEPSPs,FL,GFP,LAMP1,IF,IgG,IHC,IL-1β,IL-6,Lgmn,LOAD,LTP,LV,LXR,MAPT,MKK,MW,MWM,NFT,PHFs,PP2A,PPR,RT-qPCR,SET,shRNA,shCt,shC/EBPβ,TBS,ThS, or ThioS,TNFα,Veh,VLDL,WB,WT

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