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

doi:10.1006/mcne.2000.0910

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

SIT Research Laboratories

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	708-723
Number of pages	16
Journal	Molecular and Cellular Neuroscience
Volume	16
Issue number	6
DOIs	https://doi.org/10.1006/mcne.2000.0910
Publication status	Published - 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

Antibody-regulated neurotoxic function of cell-surface β-amyloid precursor protein. / Sudo, Haruka; Jiang, Hong; Yasukawa, Takashi; Hashimoto, Yuichi; Niikura, Takako; Kawasumi, Masaoki; Matsuda, Shuji; Takeuchi, Yuji; Aiso, Sadakazu; Matsuoka, Masaaki; Murayama, Yoshitake; Nishimoto, Ikuo.

In: Molecular and Cellular Neuroscience, Vol. 16, No. 6, 01.01.2000, p. 708-723.

Research output: Contribution to journal › Article

Sudo, Haruka ; Jiang, Hong ; Yasukawa, Takashi ; Hashimoto, Yuichi ; Niikura, Takako ; Kawasumi, Masaoki ; Matsuda, Shuji ; Takeuchi, Yuji ; Aiso, Sadakazu ; Matsuoka, Masaaki ; Murayama, Yoshitake ; Nishimoto, Ikuo. / Antibody-regulated neurotoxic function of cell-surface β-amyloid precursor protein. In: Molecular and Cellular Neuroscience. 2000 ; Vol. 16, No. 6. pp. 708-723.

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AB - 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.

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