The modeling of Alzheimer's disease by the overexpression of mutant Presenilin 1 in human embryonic stem cells.

Autor: Honda M; Stem Cell and Drug Discovery Institute, Kyoto 600-8813, Japan., Minami I; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan., Tooi N; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan., Morone N; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan., Nishioka H; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan., Uemura K; Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan., Kinoshita A; School of Human Health Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan., Heuser JE; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan; Department of Cell Biology, Washington University, St. Louis, MO 63110, USA., Nakatsuji N; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan; Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan., Aiba K; Stem Cell and Drug Discovery Institute, Kyoto 600-8813, Japan; Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan. Electronic address: kaiba@icems.kyoto-u.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2016 Jan 15; Vol. 469 (3), pp. 587-92. Date of Electronic Publication: 2015 Dec 10.
DOI: 10.1016/j.bbrc.2015.12.025
Abstrakt: 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-β 42 (Aβ42)/Aβ40 and Aβ43/Aβ40. 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.
(Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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