Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation
Amyloid β induces neuronal cell death through ROS-mediated ASK1 activation
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DOI：
10.1038/sj.cdd.4401528
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发表时间：
2005-01-01
影响因子：
12.4
通讯作者：
Ichijo, H
中科院分区：
文献类型：
--
作者：
Kadowaki, H;Nishitoh, H;Ichijo, H
淀粉样蛋白β（Abeta）是阿尔茨海默病中老年斑的主要成分，并诱导神经元细胞死亡。活性氧（ROS）、一氧化氮和内质网（ER）应激与Abeta诱导的神经毒性有关。我们已经报道了凋亡信号调节激酶1（ASK 1）是ROS和ER应激诱导的JNK激活和凋亡所必需的。在这里，我们展示了ASK 1参与Abeta诱导的神经元细胞死亡。在培养的神经细胞中，Abeta主要通过产生ROS而不是通过ER应激来激活ASK 1。重要的是，ASK 1（-/-）神经元在Abeta诱导的JNK激活和细胞死亡中有缺陷。这些结果表明ROS介导的ASK 1激活是Abeta诱导的神经毒性的关键机制，其在阿尔茨海默病中起核心作用。
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.