Title

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

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

12-14-2004

Document Type

Article

Medical Subject Headings

Alzheimer Disease; Amyloid beta-Peptides; Animals; Cell Death; Endoplasmic Reticulum; Enzyme Activation; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinase 5; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Nitrogen Oxides; PC12 Cells; Peptide Fragments; Protein-Serine-Threonine Kinases; Rats; Reactive Oxygen Species; eIF-2 Kinase

Disciplines

Genetics and Genomics

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.

Rights and Permissions

Citation: Cell Death Differ. 2005 Jan;12(1):19-24. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

15592360