4.7 Article

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

期刊

NATURE NEUROSCIENCE
卷 23, 期 12, 页码 1555-U42

出版社

NATURE PORTFOLIO
DOI: 10.1038/s41593-020-00735-y

关键词

-

资金

  1. Creative Research Initiative Program, Korean National Research Foundation (NRF) [2015R1A3A2066619]
  2. Brain Research Program through the NRF - Ministry of Science and ICT [2018M3C7A1056682, 2018M3C7A1056897]
  3. National Research Council of Science & Technology grant by the Korean government (MSIP) [CRC-15-04-KIST]
  4. Korean Institute of Science and Technology (KIST) [2E28411]
  5. Institute for Basic Science from the Ministry of Science [IBS-R001-D2]
  6. National Institutes of Health [AG054156, NRF-2016M3C7A1904233]
  7. KIST [2E26663]
  8. Pioneering Funding Award - Cure Alzheimer's Fund
  9. NIH [AG059236-01A1]
  10. National Honor Scientist Program [NRF-2012R1A3A1050385]
  11. Bio & Medical Technology Development Program [NRF-2019M3E5D2A01066259]
  12. National Research Foundation of Korea [2018M3C7A1056897, 5120201413813] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

向作者/读者索取更多资源

Chun et al. find that a severe model of reactive astrocytes overproduces hydrogen peroxide, leading to the development of Alzheimer's disease-like pathologies, including neurodegeneration, tauopathy and memory impairment. 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据