Wnt-3a overcomes β-amyloid toxicity in rat hippocampal neurons
Wnt-3a overcomes β-amyloid toxicity in rat hippocampal neurons
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DOI：
10.1016/j.yexcr.2004.02.028
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发表时间：
2004-07-01
影响因子：
3.7
通讯作者：
Inestrosa, NC
中科院分区：
文献类型：
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作者：
Alvarez, AR;Godoy, JA;Inestrosa, NC
本研究的目的是评估Wnt信号通路的内源性Wnt-3a配体的直接激活是否阻止淀粉样β肽（Abeta）诱导的大鼠海马神经元的毒性作用。我们在此报道，Wnt-3a配体确实能够克服海马神经元中Abeta诱导的毒性作用，包括对细胞存活的神经元损伤、糖原合成酶激酶-3 β（GSK-3 β）和tau磷酸化的增加、细胞质β-连环蛋白的减少和Wnt靶基因engrailed-1的表达的减少。我们进一步证明Wnt-3a保护海马神经元免受Abeta诱导的细胞凋亡。我们的研究结果支持了Wnt信号功能丧失可能在神经退行性疾病如阿尔茨海默病的进展中发挥作用的假设。(C)2004年爱思唯尔公司All rights reserved.
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.