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

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dc.contributor.authorFarías, GG
dc.contributor.authorGodoy, JA
dc.contributor.authorVázquez, MC
dc.contributor.authorAdani, R
dc.contributor.authorMeshulam, H
dc.contributor.authorAvila, J
dc.contributor.authorAmitai, G
dc.contributor.authorInestrosa, NC
dc.date.accessioned2025-01-21T01:07:11Z
dc.date.available2025-01-21T01:07:11Z
dc.date.issued2005
dc.description.abstractChanges 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.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.nbd.2004.09.012
dc.identifier.eissn1095-953X
dc.identifier.issn0969-9961
dc.identifier.urihttps://doi.org/10.1016/j.nbd.2004.09.012
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96288
dc.identifier.wosidWOS:000226452500017
dc.issue.numero1
dc.language.isoen
dc.pagina.final183
dc.pagina.inicio176
dc.revistaNeurobiology of disease
dc.rightsacceso restringido
dc.subjectAlzheimer disease
dc.subjectA beta neurotoxicity
dc.subjectanti-inflammatory ibuprofen
dc.subjectChE inhibitor pyridostigmine
dc.subjectGSK-3 beta overexpression
dc.subjectWnt signaling
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleThe anti-inflammatory and cholinesterase inhibitor bifunctional compound IBU-PO protects from β-amyloid neurotoxicity by acting on Wnt signaling components
dc.typeartículo
dc.volumen18
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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