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- Title
Amyloid beta induces neuronal cell death through ROS-mediated ASK1 activation.
- Authors
Kadowaki, H; Nishitoh, H; Urano, F; Sadamitsu, C; Matsuzawa, A; Takeda, K; Masutani, H; Yodoi, J; Urano, Y; Nagano, T; Ichijo, H
- Abstract
Amyloid beta (Abeta) 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 Abeta-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 Abeta-induced neuronal cell death. Abeta activated ASK1 mainly through production of ROS but not through ER stress in cultured neuronal cells. Importantly, ASK1-/- neurons were defective in Abeta-induced JNK activation and cell death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for Abeta-induced neurotoxicity, which plays a central role in Alzheimer's disease.
- Publication
Cell death and differentiation, 2005, Vol 12, Issue 1, p19
- ISSN
1350-9047
- Publication type
Journal Article
- DOI
10.1038/sj.cdd.4401528