期刊
EXPERIMENTAL CELL RESEARCH
卷 297, 期 1, 页码 186-196出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2004.02.028
关键词
amyloid; neurotoxicity; win signaling; GSK-3 beta; engrailed; apoptosis; Alzheimer's disease
The aim of this study was to evaluate whether the direct activation of the Wnt signaling pathway by its endogenous Wnt-3a ligand prevents the toxic effects induced by amyloid-beta-peptide (Abeta) in rat hippocampal neurons. We report herein that the Wnt-3a ligand was indeed able to overcome toxic effects induced by Abeta in hippocampal neurons, including a neuronal impairment on cell survival, an increase in glycogen synthase kinase-3beta (GSK-3beta) and tau phosphorylation, a decrease in cytoplasmic beta-catenin and a decrease in the expression of the Wnt target gene engrailed-1. We further demonstrate that Wnt-3a protects hippocampal neurons from apoptosis induced by Abeta. Our results support the hypothesis that a loss of function of Wnt signaling may play a role in the progression of neurodegenerative diseases such as Alzheimer's disease. (C) 2004 Elsevier Inc. All rights reserved.
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