The role of LINC00094/miR-224-5p (miR-497-5p)/Endophilin-1 axis in Memantine mediated protective effects on blood-brain barrier in AD microenvironment.

This study was performed to demonstrate the role of the MEM in regulating BBB permeability in AD microenvironment as well as its possible mechanisms. The present study showed that LINC00094 was dramatically increased in Abeta1-42 -incubated microvascular endothelial cells (ECs) of BBB model in vitro. Besides, it was decreased in MEM-incubated ECs. Silencing LINC00094 significantly decreased BBB permeability, meanwhile up-regulating the expression of ZO-1, occludin and claudin-5. Furthermore, silencing LINC00094 enhance the effect of MEM on decreasing BBB permeability in AD microenvironment. The analysis of the mechanism demonstrated that reduction of LINC00094 inhibited Endophilin-1 expression by up-regulating miR-224-4p/miR-497-5p, promoted the expression of ZO-1, occludin and claudin-5, and ultimately alleviated BBB permeability in AD microenvironment. Taken together, the present study suggests that the MEM/LINC00094/miR-224-5p (miR-497-5p)/Endophilin-1 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment. Silencing LINC00094 combined with MEM provides a novel target for the therapy of AD.
PMID: 30801976 [PubMed - as supplied by publisher]

Source: J Cell Mol Med - February 22, 2019 Category: Molecular Biology Authors: Zhu L, Lin M, Ma J, Liu W, Gao L, Wei S, Xue Y, Shang X Tags: J Cell Mol Med Source Type: research