V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders

Takako Niikura, Norie Murayama, Yu Ichi Hashimoto, Yuko Ito, Yohichi Yamagishi, Masaaki Matsuoka, Yuji Takeuchi, Sadakazu Aiso, Ikuo Nishimoto

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)445-454
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume274
Issue number2
DOIs
Publication statusPublished - 2000 Aug 2

    Fingerprint

Keywords

  • Alzheimer's disease
  • Amyloid precursor protein
  • Anti-risk factor
  • Apoptosis
  • Caspase inhibitor
  • Disease mutation
  • Ecdysone-inducible system
  • Electron microscopy
  • Neuronal death
  • Pertussis toxin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Niikura, T., Murayama, N., Hashimoto, Y. I., Ito, Y., Yamagishi, Y., Matsuoka, M., Takeuchi, Y., Aiso, S., & Nishimoto, I. (2000). V642I APP-inducible neuronal cells: A model system for investigating Alzheimer's disorders. Biochemical and Biophysical Research Communications, 274(2), 445-454. https://doi.org/10.1006/bbrc.2000.3143