期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 469, 期 3, 页码 587-592出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.12.025
关键词
Human embryonic stem cell; Alzheimer's disease; Cellular disease model; Presenilin 1; Synaptic dysfunction
资金
- New Energy and Industrial Technology Development Organization
- New Energy and Industrial Technology Development Organization [P05010]
- iCeMS
- World Premier International Research Center Initiative (WPI), MEXT, Japan
Cellular disease models are useful tools for Alzheimer's disease (AD) research. Pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), are promising materials for creating cellular models of such diseases. In the present study, we established cellular models of AD in hESCs that overexpressed the mutant Presenilin 1 (PS1) gene with the use of a site specific gene integration system. The overexpression of PS1 did not affect the undifferentiated status or the neural differentiation ability of the hESCs. We found increases in the ratios of amyloid-beta 42 (A beta 42)/ A beta 40 and A beta 43/A beta 40. Furthermore, synaptic dysfunction was observed in a cellular model of AD that overexpressed mutant PS1. These results suggest that the AD phenotypes, in particular, the electrophysiological abnormality of the synapses in our AD models might be useful for AD research and drug discovery. (C) 2015 The Authors. Published by Elsevier Inc.
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