English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/115984
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Effects of a tacrine-8-hydroxyquinoline hybrid (IQM-622) on Aβ accumulation and cell death: Involvement in hippocampal neuronal loss in Alzheimer's disease

AuthorsAntequera, Desiree; Bolós, Marta; Spuch, Carlos; Pascual, Consuelo; Ferrer, Isidro; Fernández-Bachiller, María Isabel ; Rodríguez-Franco, María Isabel ; Carro, Eva
KeywordsAlzheimer's disease
Transgenic mice
Neuroprotection
Domoic acid
Aβ degradation
Acetylcholinesterase inhibitors
Issue Date2012
PublisherAcademic Press
CitationNeurobiology of Disease 46: 682-691 (2012)
AbstractSeveral studies have implicated the enzyme acetylcholinesterase (AChE) as well as several biometals in the pathogenesis of Alzheimer's disease (AD). A multifunctional molecule, the hybrid tacrine-8-hydroxyquinoline (named IQM-622), displays cholinergic, antioxidant, copper-complexing and neuroprotective properties. Using in vitro and in vivo models, we investigated the modulating effects of IQM-622 on amyloid β-protein (Aβ)-induced pathology as well as on chemically induced neurodegeneration by domoic acid. In the first experimental model, we observed a significant decrease in brain Aβ deposits in IQM-622-treated APP/Ps1 mice for four weeks. Moreover, IQM-622 promoted the degradation of intracellular Aβ in astrocytes, and protected against Aβ toxicity in cultured astrocytes and neurons. These findings suggest that the neuroprotective effect of IQM-622 is not only related to AChE inhibition, but also involves other mechanisms, including the modulation of Aβ-degradation pathways in AD brain. In this study we also compare the neuronal loss in CA1 hippocampal field of AD patients and of mice treated with domoic acid, giving similar patterns. Thus, we used a second experimental model by killing hippocampal neurons by domoic acid damage, in which IQM-622 increased survival in the CA1 and dentate gyrus regions of the hippocampus. Our observations suggest that administration of IQM-622 may have significant beneficial effects in neurodegenerative diseases, including AD, which course with acute or progressive neuronal death.
URIhttp://hdl.handle.net/10261/115984
DOI10.1016/j.nbd.2012.03.009
Identifiersdoi: 10.1016/j.nbd.2012.03.009
issn: 0969-9961
e-issn: 1095-953X
Appears in Collections:(IQM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.