RT Journal Article
SR Electronic
T1 TRA2A-induced upregulation of LINC00662 regulates blood-brain barrier permeability by affecting ELK4 mRNA stability in Alzheimer’s microenvironment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 848408
DO 10.1101/848408
A1 Qianshuo Liu
A1 Lu Zhu
A1 Xiaobai Liu
A1 Jian Zheng
A1 Yunhui Liu
A1 Xuelei Ruan
A1 Shuo Cao
A1 Heng Cai
A1 Zhen Li
A1 Yixue Xue
YR 2019
UL http://biorxiv.org/content/early/2019/11/20/848408.abstract
AB The blood-brain barrier (BBB) has an important significance in maintenance and regulation of the neural microenvironment. The occurrence of BBB disruption is the pathological change of early Alzheimer’s disease (AD). RNA-binding proteins and long non-coding RNAs are closely related to the regulation of BBB permeability. Our study was performed to demonstrate TRA2A/LINC00662/ELK4 axis that regulates BBB permeability in AD microenvironment. In Aβ1-42-incubated microvascular endothelial cells (ECs) of BBB model in vitro, TRA2A and LINC00662 were enriched. TRA2A increased the stability of LINC00662 by binding with it. The knockdown of either TRA2A or LINC00662 decreased the BBB permeability via upregulating the levels of tight junction-related proteins. ELK4 was downregulated in BBB model in vitro in AD microenvironment. LINC00662 mediated the degradation of ELK4 mRNA by SMD pathway. The downregulated ELK4 increased the permeability of BTB by inducing the tight junction-related proteins. TRA2A/LINC00662/ELK4 axis is important in the regulation of BBB permeability in AD microenvironment, which would be a new molecular target for AD treatment.