Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2- production

Title
Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2- production
Authors
박기덕박종현이승은류훈조혜선임현주Heejung ChunYou Jung Kang김윤하Jin Hee ShinWoojin WonJiwoon LimYeonha JuYongmin Mason ParkSunpil Kim이재광우준성황은진조선미Daesoo KimDoo Yeon KimJeong-Sun SeoByoung Joo GwagYoung Soo KimBong-Kiun KaangHansang Cho이창준
Issue Date
2020-11
Publisher
Nature neuroscience
Citation
VOL 23, NO 11-1566
Abstract
Although the pathological contributions of reactive astrocytes have been implicated in Alzheimer’s disease (AD), their in vivo functions remain elusive due to the lack of appropriate experimental models and precise molecular mechanisms. Here, we show the importance of astrocytic reactivity on the pathogenesis of AD using GiD, a newly developed animal model of reactive astrocytes, where the reactivity of astrocytes can be manipulated as mild (GiDm) or severe (GiDs). Mechanistically, excessive hydrogen peroxide (H2O2) originated from monoamine oxidase B in severe reactive astrocytes causes glial activation, tauopathy, neuronal death, brain atrophy, cognitive impairment and eventual death, which are significantly prevented by AAD-2004, a potent H2O2 scavenger. These H2O2?-induced pathological features of AD in GiDs are consistently recapitulated in a three-dimensional culture AD model, virus-infected APP/PS1 mice and the brains of patients with AD. Our study identifies H2O2 from severe but not mild reactive astrocytes as a key determinant of neurodegeneration in AD.
URI
http://pubs.kist.re.kr/handle/201004/72326
ISSN
1097-6256
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

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

BROWSE