Antibody-regulated neurotoxic function of cell-surface β-amyloid precursor protein

Haruka Sudo, Hong Jiang, Takashi Yasukawa, Yuichi Hashimoto, Takako Niikura, Masaoki Kawasumi, Shuji Matsuda, Yuji Takeuchi, Sadakazu Aiso, Masaaki Matsuoka, Yoshitake Murayama, Ikuo Nishimoto

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54 Citations (Scopus)

Abstract

APP is a transmembrane precursor of β-amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of normal wild-type APP (wtAPP). Treatment of neuronal F11 cells, immortalized embryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies caused death. Death was not induced by antibody in parental F11 cells, Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in primary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study provides a novel insight into the normal and pathological functions of cell-surface wtAPP.

Original languageEnglish
Pages (from-to)708-723
Number of pages16
JournalMolecular and Cellular Neuroscience
Volume16
Issue number6
DOIs
Publication statusPublished - 2000 Jan 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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    Sudo, H., Jiang, H., Yasukawa, T., Hashimoto, Y., Niikura, T., Kawasumi, M., Matsuda, S., Takeuchi, Y., Aiso, S., Matsuoka, M., Murayama, Y., & Nishimoto, I. (2000). Antibody-regulated neurotoxic function of cell-surface β-amyloid precursor protein. Molecular and Cellular Neuroscience, 16(6), 708-723. https://doi.org/10.1006/mcne.2000.0910