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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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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.
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참고문헌 (25)
참고문헌 신청
Andres RH / 2011 / Human neural stem cells enhance structural plasticity and axonal transport in the ischaemic brain / Brain 134 : 1777 ~ 1789
Breunig JJ / 2011 / Neural stem cells: historical perspective and future prospects / Neuron 70 : 614 ~ 625
Cleary JP / 2005 / Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function / Nat Neurosci 8 : 79 ~ 84
Cummings BJ / 2005 / Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice / Proc Natl Acad Sci USA 102 : 14069 ~ 14074
Haass C / 2007 / Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide / Nat Rev Mol Cell Biol 8 : 101 ~ 112
Breunig JJ / 2011 / Neural stem cells: historical perspective and future prospects / Neuron 70 : 614 ~ 625
Cleary JP / 2005 / Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function / Nat Neurosci 8 : 79 ~ 84
Cummings BJ / 2005 / Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice / Proc Natl Acad Sci USA 102 : 14069 ~ 14074
Haass C / 2007 / Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide / Nat Rev Mol Cell Biol 8 : 101 ~ 112
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