| Title : The anti-inflammatory and cholinesterase inhibitor bifunctional compound IBU-PO protects from beta-amyloid neurotoxicity by acting on Wnt signaling components - Farias_2005_Neurobiol.Dis_18_176 |
| Author(s) : Farias GG , Godoy JA , Vazquez MC , Adani R , Meshulam H , Avila J , Amitai G , Inestrosa NC |
| Ref : Neurobiol Dis , 18 :176 , 2005 |
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Abstract :
Changes in signal transduction are implicated in neuronal responses to the Alzheimer's amyloid-beta-peptide (Abeta), 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 microM) inhibits glycogen-synthase-kinase-3beta (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 Abeta1-40 in rat hippocampal neurons. |
| PubMedSearch : Farias_2005_Neurobiol.Dis_18_176 |
| PubMedID: 15649708 |
Farias GG, Godoy JA, Vazquez MC, Adani R, Meshulam H, Avila J, Amitai G, Inestrosa NC (2005)
The anti-inflammatory and cholinesterase inhibitor bifunctional compound IBU-PO protects from beta-amyloid neurotoxicity by acting on Wnt signaling components
Neurobiol Dis
18 :176
Farias GG, Godoy JA, Vazquez MC, Adani R, Meshulam H, Avila J, Amitai G, Inestrosa NC (2005)
Neurobiol Dis
18 :176