TREM2 promotes A beta phagocytosis by upregulating C/EBP alpha-dependentCD36 expression in microglia

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/486506.do
DOI
10.1038/s41598-017-11634-x
Title
TREM2 promotes A beta phagocytosis by upregulating C/EBP alpha-dependentCD36 expression in microglia
Description
This work was supported by Basic Science Research Program through theNational Research Foundation of Korea (NRF) funded by the Ministry ofScience, the ICT & Future Planning (NRF-2015R1A2A2A01007855) and fundedby the Ministry of Education (2016R1D1A3B03931710, WSC).
abstract
TREM2 plays a critical role in the alleviation of Alzheimer's disease by promoting A beta phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of A beta remains to be revealed. We found that learning and memory functions were improved in aged TREM2 TG mice, with the opposite effects in KO mice. The amount of phagocytosed A beta was significantly reduced in the primary microglia of KO mice. CD36 expression in primary microglia was greater in TG than in WT mice but was substantially decreased in KO mice. The expression of C/EBP alpha, an upstream transcriptional activator of CD36, was also elevated in primary microglia of TG mice but decreased in KO mice. The transcription of CD36 was markedly increased by TREM2 overexpression, and this effect was suppressed by a mutation of the C/EBP alpha binding site on the CD36 promoter. The TREM2-induced expression of CD36 and C/EBP alpha was inhibited by treatment with PI3K/AKT signaling blockers, and phosphorylation of AKT was elevated in TREM2-overexpressing BV2 cells. The present study provides evidence that TREM2 is required for preventing loss of memory and learning in Alzheimer's disease by regulating C/EBP alpha-dependent CD36 expression and the consequent A beta phagocytosis.
provenance
Made available in Cube on 2018-09-28T16:09:26Z (GMT). No. of bitstreams: 0
language
English
author
Kim, Su-Man
Mun, Bo-Ram
Lee, Sun-Jun
Joh, Yechan
Lee, Hwa-Youn
Ji, Kon-Young
Choi, Ha-Rim
Lee, Eun-Hee
Kim, Eun-Mi
Jang, Ji-Hye
Song, Hyeong-Woo
Mook-Jung, Inhee
Choi, Won-Seok
Kang, Hyung-Sik
accessioned
2018-09-28T16:09:26Z
available
2018-09-28T16:09:26Z
issued
2017
citation
SCIENTIFIC REPORTS(7)
issn
2045-2322
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/486506.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274284
Jurisdiction
Rep.of Korea
Project Name
Higher Education Team for Bioregulator Research
rights
openAccess
type
article


Files in This Item

There are no attached files.