The central goal of this project is to study several actions of AChEI not related with the main mechanism of these drugs /actylcholinesterase inhibition) that can participate in the improvement observed in the long term treatment of Alzheimer's disease patients. The drugs that will be used in this study, huprines (...). The following points will be studied: a) interaction of the dimeric compounds with nicotinic receptors and their regulation in vitro (huprines and dimeric compounds) and in vivo (huprines); b) action of the different AChEI over the secretion of sAPP and the transduction pathways and receptors implicated in both PC12 cells and isolated minisprisms; c) in vivo study in triple transgenic 3cTg-AD mice on the action of huprines over both the sAPP secretion and the PKC and MAPK expression in cerebral cortex; d) characterization of the prionic protein aggregation induced by AChE and its inhibition by several AChEI; e) determination of the neuroprotective effect of AChEI against the actions of both \beta-amyloid and PrP106-126 proteins and its relationship with nicotinic receptors in PC12 cells and f) determination of neuroprotective effects of the AChEI, after serum deprivation, and its relationship with the apoptotic pathways in PC12 cells and the participation of both PKC and MAPK.
|Effective start/end date||1/10/06 → 30/09/09|
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