TY - JOUR
T1 - Antibody-regulated neurotoxic function of cell-surface β-amyloid precursor protein
AU - Sudo, Haruka
AU - Jiang, Hong
AU - Yasukawa, Takashi
AU - Hashimoto, Yuichi
AU - Niikura, Takako
AU - Kawasumi, Masaoki
AU - Matsuda, Shuji
AU - Takeuchi, Yuji
AU - Aiso, Sadakazu
AU - Matsuoka, Masaaki
AU - Murayama, Yoshitake
AU - Nishimoto, Ikuo
N1 - Funding Information:
We thank Yasuko Homma and Ugo Giambarella for indispensable technical assistance; Yeqi Yao for help to the construction of APPED cDNA; Kazuaki Yoshikawa for his kind gift of Bu695; John T. Potts Jr., Mark C. Fishman, and Shigeaki Kato for helping us with this study and for critically reading the manuscript; Yumi and Yoshiomi Tamai for support; Ko-ichi Tsuchiya, Kazumi Nishihara, and other department members for essential cooperation; and Dovie Wylie for technical assistance. We are especially indebted to Takako Hiraki and Keisuke Kouyama for expert technical assistance. This work was supported in part by grants from the Naito Foundation, Brain Science Foundation, Takeda Medical Research Foundation, Takeda Science Foundation, Keio University Grant-in-Aid for Encouragement of Young Medical Scientists 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 OPSR.
PY - 2000
Y1 - 2000
N2 - 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.
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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U2 - 10.1006/mcne.2000.0910
DO - 10.1006/mcne.2000.0910
M3 - Article
C2 - 11124892
AN - SCOPUS:0034525215
VL - 16
SP - 708
EP - 723
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 6
ER -