Browsing by Author "Vázquez, MC"

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    The anti-inflammatory and cholinesterase inhibitor bifunctional compound IBU-PO protects from β-amyloid neurotoxicity by acting on Wnt signaling components
    (2005) Farías, GG; Godoy, JA; Vázquez, MC; Adani, R; Meshulam, H; Avila, J; Amitai, G; Inestrosa, NC
    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.