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Amyloid-β oligomers regulate the properties of human neural stem cells through GSK-3β signaling

Authors
 Il-Shin Lee  ;  Kwangsoo Jung  ;  Il-Sun Kim  ;  Kook In Park 
Citation
 Experimental and Molecular Medicine, Vol.45(11) : 60-60, 2013 
Journal Title
 Experimental and Molecular Medicine 
ISSN
 1226-3613 
Issue Date
2013
Abstract
Alzheimer's disease (AD) is the most common cause of age-related dementia. The neuropathological hallmarks of AD include extracellular deposition of amyloid-β peptides and neurofibrillary tangles that lead to intracellular hyperphosphorylated tau in the brain. Soluble amyloid-β oligomers are the primary pathogenic factor leading to cognitive impairment in AD. Neural stem cells (NSCs) are able to self-renew and give rise to multiple neural cell lineages in both developing and adult central nervous systems. To explore the relationship between AD-related pathology and the behaviors of NSCs that enable neuroregeneration, a number of studies have used animal and in vitro models to investigate the role of amyloid-β on NSCs derived from various brain regions at different developmental stages. However, the Aβ effects on NSCs remain poorly understood because of conflicting results. To investigate the effects of amyloid-β oligomers on human NSCs, we established amyloid precursor protein Swedish mutant-expressing cells and identified cell-derived amyloid-β oligomers in the culture media. Human NSCs were isolated from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres. Human NSCs exposure to cell-derived amyloid-β oligomers decreased dividing potential resulting from senescence through telomere attrition, impaired neurogenesis and promoted gliogenesis, and attenuated mobility. These amyloid-β oligomers modulated the proliferation, differentiation and migration patterns of human NSCs via a glycogen synthase kinase-3β-mediated signaling pathway. These findings contribute to the development of human NSC-based therapy for AD by elucidating the effects of Aβ oligomers on human NSCs.
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DOI
10.1038/emm.2013.125
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
김일선(Kim, Il-Sun) ORCID logo https://orcid.org/0000-0003-4033-4323
박국인(Park, Kook In) ORCID logo https://orcid.org/0000-0001-8499-9293
이일신(Lee, Il Shin)
정광수(Jung, Kwang Soo) ORCID logo https://orcid.org/0000-0001-7365-7247
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88724
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