气候变化领域集成服务门户(CCPortal): Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity

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DOI	10.1073/PNAS.2011876118
	Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity
	Ippati S.; Deng Y.; Van Der Hoven J.; Heu C.; Van Hummel A.; Chua S.W.; Paric E.; Chan G.; Feiten A.; Fath T.; Ke Y.D.; Haass N.K.; Ittner L.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	Neurons are postmitotic cells. Reactivation of the cell cycle by neurons has been reported in Alzheimer's disease (AD) brains and models. This gave rise to the hypothesis that reentering the cell cycle renders neurons vulnerable and thus contributes to AD pathogenesis. Here, we use the fluorescent ubiquitination-based cell cycle indicator (FUCCI) technology to monitor the cell cycle in live neurons. We found transient, self-limited cell cycle reentry activity in naive neurons, suggesting that their postmitotic state is a dynamic process. Furthermore, we observed a diverse response to oligomeric amyloid-β (oAβ) challenge; neurons without cell cycle reentry activity would undergo cell death without activating the FUCCI reporter, while neurons undergoing cell cycle reentry activity at the time of the oAβ challenge could maintain and increase FUCCI reporter signal and evade cell death. Accordingly, we observed marked neuronal FUCCI positivity in the brains of human mutant Aβ precursor protein transgenic (APP23) mice together with increased neuronal expression of the endogenous cell cycle control protein geminin in the brains of 3-mo-old APP23 mice and human AD brains. Taken together, our data challenge the current view on cell cycle in neurons and AD, suggesting that pathways active during early cell cycle reentry in neurons protect from Aβ toxicity. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Alzheimer; Cell cycle; FUCCI; Postmitotic neurons
语种	英语
scopus关键词	amyloid beta protein; amyloid precursor protein; geminin; Alzheimer disease; animal cell; animal experiment; animal tissue; Article; cell cycle; cell cycle assay; cell cycle reentry; cell death; controlled study; embryo; female; fluorescent ubiquitination based cell cycle indicator; human; human tissue; mitosis; mouse; nerve cell; neuroprotection; neurotoxicity; nonhuman; priority journal; protein expression
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180203
作者单位	Dementia Research Centre, Department of Biomedical Sciences, Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, NSW 2109, Australia; San Raffaele Scientific Institute, San Raffaele Hospital, Milan, 20132, Italy; Biomedical Imaging Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia; University of Queensland, Diamantina Institute, University of Queensland, Brisbane, QLD 4102, Australia
推荐引用方式 GB/T 7714	Ippati S.,Deng Y.,Van Der Hoven J.,et al. Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity[J],2021,118(12).
APA	Ippati S..,Deng Y..,Van Der Hoven J..,Heu C..,Van Hummel A..,...&Ittner L.M..(2021).Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Ippati S.,et al."Rapid initiation of cell cycle reentry processes protects neurons from amyloid-β toxicity".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).