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

• Published in: Experimental & molecular medicine pp. 1 - 15
• Main Authors: 이일신, 정광수, 김일선, 박국인
• Format: Journal Article
• Language: English
• Published: 생화학분자생물학회 01.11.2013
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

Alzheimer’s disease (AD) is the most common cause of age-related dementia. The neuropathological hallmarks of AD include extracellular deposition of amyloid-b peptides and neurofibrillary tangles that lead to intracellular hyperphosphorylated tau in the brain. Soluble amyloid-b 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-b on NSCs derived from various brain regions at different developmental stages. However, the Ab effects on NSCs remain poorly understood because of conflicting results. To investigate the effects of amyloid-b oligomers on human NSCs, we established amyloid precursor protein Swedish mutant-expressing cells and identified cell-derived amyloid-b 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-b oligomers decreased dividing potential resulting from senescence through telomere attrition, impaired neurogenesis and promoted gliogenesis, and attenuated mobility. These amyloid-b oligomers modulated the proliferation, differentiation and migration patterns of human NSCs via a glycogen synthase kinase-3b-mediated signaling pathway. These findings contribute to the development of human NSC-based therapy for AD by elucidating the effects of Ab oligomers on human NSCs. KCI Citation Count: 30