Detailed Information

Cited 0 time in webofscience Cited 96 time in scopus
Metadata Downloads

Microrna-33 regulates apoe lipidation and amyloid-β metabolism in the brain

Authors
Kim J.Yoon H.Horie T.Burchett J.M.Restivo J.L.Rotllan N.Ramirez C.M.Verghese P.B.Ihara M.Hoe H.-S.Esau C.Fernandez-Hernando C.Holtzman D.M.Cirrito J.R.Ono K.Kim J.
Issue Date
Nov-2015
Publisher
Society for Neuroscience
Citation
Journal of Neuroscience, v.35, no.44, pp.14717 - 14726
Journal Title
Journal of Neuroscience
Volume
35
Number
44
Start Page
14717
End Page
14726
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/870
ISSN
0270-6474
Abstract
Dysregulation of amyloid-β (Aβ) metabolism is critical for Alzheimer’s disease (AD) pathogenesis. Mounting evidence suggests that apolipoprotein E (ApoE) is involved in Aβ metabolism. ATP-binding cassette transporter A1 (ABCA1) is a key regulator of ApoE lipidation, which affects Aβ levels. Therefore, identifying regulatory mechanisms of ABCA1 expression in the brain may provide new therapeutic targets for AD. Here, we demonstrate that microRNA-33 (miR-33) regulates ABCA1 and Aβ levels in the brain. Overexpression of miR-33 impaired cellular cholesterol efflux and dramatically increased extracellular Aβ levels by promoting Aβ secretion and impairing Aβ clearance in neural cells. In contrast, genetic deletion of mir-33 in mice dramatically increased ABCA1 levels and ApoE lipidation, but it decreased endogenous Aβ levels in cortex. Most importantly, pharmacological inhibition of miR-33 via antisense oligonucleotide specifically in the brain markedly decreased Aβ levels in cortex of APP/PS1 mice, representing a potential therapeutic strategy for AD.
Files in This Item
There are no files associated with this item.
Appears in
Collections
연구본부 > 퇴행성 뇌질환 연구그룹 > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Hoe, Hyang Sook photo

Hoe, Hyang Sook
연구본부 (퇴행성뇌질환 연구그룹)
Read more

Altmetrics

Total Views & Downloads

BROWSE