Journal
CELL DEATH AND DIFFERENTIATION
Volume 12, Issue 1, Pages 19-24Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401528
Keywords
amyloid beta; ASK1; JNK; reactive oxygen species (ROS); neuronal cell death
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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.
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