The anti-inflammatory and cholinesterase inhibitor bifunctional compound IBU-PO protects from β-amyloid neurotoxicity by acting on Wnt signaling components

被引：35

作者：

Farías, GG

Godoy, JA

Vázquez, MC

Adani, R

Meshulam, H

Avila, J

Amitai, G

Inestrosa, NC

机构：

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

[2] IIBR, Dept Pharmacol, IL-74100 Ness Ziona, Israel

[3] Univ Autonoma Madrid, CSIC, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain

来源：

NEUROBIOLOGY OF DISEASE | 2005年 / 18卷 / 01期

关键词：

Alzheimer disease; A beta neurotoxicity; anti-inflammatory ibuprofen; ChE inhibitor pyridostigmine; GSK-3 beta overexpression; Wnt signaling;

D O I：

10.1016/j.nbd.2004.09.012

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Changes in signal transduction are implicated in neuronal responses to the Alzheimer's amyloid-beta-peptide (A), which include neurotransmitter systems and pathways involved in the maintenance of the nervous system. We report here that a new bifunctional compound IBU-PO, which combines a non-steroidal anti-inflammatory drug (NSAID) (Ibuprofen) and a cholinesterase (ChE) inhibitor (Octyl-Pyridostigmine), is neuroprotective against Abeta-neurotoxicity, and its activity is associated to Wnt signaling components in rat hippocampal and mouse cortical neurons. IBU-PO (0.01-1 muM) inhibits glycogen-synthase-kinase-3 (GSK-3beta) and stabilizes cytoplasmic beta-catenin reverting the silencing of the Wnt pathway caused by Abeta-toxicity and GSK-3beta overexpression. In addition, IBU-PO enhances, dose-dependently, the non-amyloidogenic amyloid precursor protein (APP) cleavage by increasing secreted APP and decreasing endogenous Abeta(1-40) in rat hippocampal neurons. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：176 / 183

页数：8

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