Antequera_2012_Neurobiol.Dis_46_682

Reference

Title : Effects of a tacrine-8-hydroxyquinoline hybrid (IQM-622) on Abeta accumulation and cell death: involvement in hippocampal neuronal loss in Alzheimer's disease - Antequera_2012_Neurobiol.Dis_46_682
Author(s) : Antequera D , Bolos M , Spuch C , Pascual C , Ferrer I , Fernandez-Bachiller MI , Rodriguez-Franco MI , Carro E
Ref : Neurobiol Dis , 46 :682 , 2012
Abstract :

Several 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 beta-protein (Abeta)-induced pathology as well as on chemically induced neurodegeneration by domoic acid. In the first experimental model, we observed a significant decrease in brain Abeta deposits in IQM-622-treated APP/Ps1 mice for four weeks. Moreover, IQM-622 promoted the degradation of intracellular Abeta in astrocytes, and protected against Abeta 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 Abeta-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.

PubMedSearch : Antequera_2012_Neurobiol.Dis_46_682
PubMedID: 22426395

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Citations formats

Antequera D, Bolos M, Spuch C, Pascual C, Ferrer I, Fernandez-Bachiller MI, Rodriguez-Franco MI, Carro E (2012)
Effects of a tacrine-8-hydroxyquinoline hybrid (IQM-622) on Abeta accumulation and cell death: involvement in hippocampal neuronal loss in Alzheimer's disease
Neurobiol Dis 46 :682

Antequera D, Bolos M, Spuch C, Pascual C, Ferrer I, Fernandez-Bachiller MI, Rodriguez-Franco MI, Carro E (2012)
Neurobiol Dis 46 :682