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Chun, Hee Jung
인지 및 사회성 연구단
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Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer's disease via H2O2-production

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Title
Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer's disease via H2O2-production
Author(s)
Heejung Chun; Im, Hyeonjoo; Kang, You Jung; Kim, Yunha; Shin, Jin Hee; Woojin Won; Jiwoon Lim; Yeonha Ju; Yongmin Mason Park; Sunpil Kim; Lee, Seung Eun; Lee, Jaekwang; Woo, Junsung; Hwang, Yujin; Cho, Hyesun; Jo, Seonmi; Park, Jong-Hyun; Kim, Daesoo; Kim, Doo Yeon; Seo, Jeong-Sun; Gwag, Byoung Joo; Kim, Young Soo; Park, Ki Duk; Kaang, Bong-Kiun; Cho, Hansang; Ryu, Hoon; ChangJoon Justin Lee
Publication Date
2020-11
Journal
NATURE NEUROSCIENCE, v.23, pp.1555 - 1566
Publisher
NATURE RESEARCH
Abstract
© the Author(s). 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 AAD2004, 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
https://pr.ibs.re.kr/handle/8788114/8922
DOI
10.1038/s41593-020-00735-y
ISSN
1097-6256
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Cognitive Glioscience Group(인지 교세포과학 그룹) > 1. Journal Papers (저널논문)
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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