Wnt-3a overcomes β-amyloid toxicity in rat hippocampal neurons

被引：215

作者：

Alvarez, AR ^{[1
]}

Godoy, JA ^{[1
]}

Mullendorff, K ^{[1
]}

Olivares, GH ^{[1
]}

Bronfman, M ^{[1
]}

Inestrosa, NC ^{[1
]}

机构：

[1] Pontificia Univ Catolica Chile, Mol Neurobiol Unit, Fac Ciencias Biol, Ctr FONDAP Regulac Celular & Patol Joaquin V Luco, Santiago, Chile

来源：

EXPERIMENTAL CELL RESEARCH | 2004年 / 297卷 / 01期

关键词：

amyloid; neurotoxicity; win signaling; GSK-3; beta; engrailed; apoptosis; Alzheimer's disease;

D O I：

10.1016/j.yexcr.2004.02.028

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：186 / 196

页数：11

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