Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation

H. Kadowaki, H. Nishitoh, F. Urano, C. Sadamitsu, A. Matsuzawa, K. Takeda, H. Masutani, J. Yodoi, Y. Urano, T. Nagano, H. Ichijo

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Amyloid β (Aβ) is a main component of senile plaques in Alzheimer's disease and induces neuronal cell death. Reactive oxygen species (ROS), nitric oxide and endoplasmic reticulum (ER) stress have been implicated in Aβ-induced neurotoxicity. We have reported that apoptosis signal-regulating kinase 1 (ASK1) is required for ROS- and ER stress-induced JNK activation and apoptosis. Here we show the involvement of ASK1 in Aβ-induced neuronal cell death. Aβ activated ASK1 mainly through production of ROS but not through ER stress in cultured neuronal cells. Importantly, ASK1-/- neurons were defective in Aβ-induced JNK activation and cell death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for Aβ-induced neurotoxicity, which plays a central role in Alzheimer's disease.

Original languageEnglish
Pages (from-to)19-24
Number of pages6
JournalCell Death and Differentiation
Issue number1
StatePublished - Jan 1 2005
Externally publishedYes


  • ASK1
  • Amyloid β
  • JNK
  • Neuronal cell death
  • Reactive oxygen species (ROS)

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    Kadowaki, H., Nishitoh, H., Urano, F., Sadamitsu, C., Matsuzawa, A., Takeda, K., Masutani, H., Yodoi, J., Urano, Y., Nagano, T., & Ichijo, H. (2005). Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation. Cell Death and Differentiation, 12(1), 19-24.