@article{68aff27cf97a4cc3877476f684d001b3,
title = "V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders",
abstract = "APP is a precursor of β amyloid deposited in Alzheimer's disease (AD). Although genetic studies established that mutations in APP cause familial AD (FAD), the mechanism for neuronal death by FAD mutants has not been well understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not vehicle, killed most cells within a few days, with rounding, shrinkage, and detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO and pertussis toxin. Electron microscopic analysis revealed that apoptosis occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the anti-AD factors estrogen and apoE2. These data demonstrate not only that expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I cells, the first neuronal cells with inducible FAD gene expression, provide a useful model system in investigating AD disorders. (C) 2000 Academic Press.",
keywords = "Alzheimer's disease, Amyloid precursor protein, Anti-risk factor, Apoptosis, Caspase inhibitor, Disease mutation, Ecdysone-inducible system, Electron microscopy, Neuronal death, Pertussis toxin",
author = "Takako Niikura and Norie Murayama and Hashimoto, {Yu Ichi} and Yuko Ito and Yohichi Yamagishi and Masaaki Matsuoka and Yuji Takeuchi and Sadakazu Aiso and Ikuo Nishimoto",
note = "Funding Information: We thank Yasuko Homma and Ugo Giambarella for indispensable technical assistance; John T. Potts Jr., Mark C. Fishman, and Shigeaki Kato for helping us with this study and critical reading; Yumi and Yoshiomi Tamai for encouragement; and Ko-ichi Tsuchiya, Kazumi Nishihara, and other department members for technical assistance. We are especially indebted to Takako Hiraki for indispensable assistance and Dovie Wylie for excellent technical assistance. This work was supported in part by grants from Naito Foundation, Brain Science Foundation, Takeda Medical Research Foundation, Takeda Science Foundation, the Ministry of Health and Welfare of Japan, the Ministry of Education, Science, and Culture of Japan and the Organization for Pharmaceutical Safety and Research. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2000",
month = aug,
day = "2",
doi = "10.1006/bbrc.2000.3143",
language = "English",
volume = "274",
pages = "445--454",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",
}