6533b821fe1ef96bd127b8b8

RESEARCH PRODUCT

Galantamine modulates nicotinic receptor and blocks Aβ-enhanced glutamate toxicity

Tomoki NakamizoHideyuki SawadaRie KankiShun ShimohamaAlfred MaelickeHirofumi YamashitaTakeshi Kihara

subject

Cell SurvivalBiophysicsGlutamic AcidReceptors NicotinicPharmacologycomplex mixturesBiochemistryNeuroprotectionmedicineGalantamineAnimalsDrug InteractionsMolecular BiologyProtein kinase BPI3K/AKT/mTOR pathwayCerebral CortexNeuronsAmyloid beta-PeptidesDose-Response Relationship DrugGalantamineChemistryGlutamate receptorNeurotoxicityCell Biologymedicine.diseaseRatsNeuroprotective AgentsNicotinic agonistnervous systemPhosphorylationmedicine.drug

description

Galantamine is a plant alkaloid that is used in the treatment of Alzheimer's disease. We have studied the effects of galantamine on beta-amyloid-enhanced glutamate toxicity using primary rat cultured cortical neurons. Nicotine and galantamine alone, and in combination, protected neurons against this neurotoxicity. The protection was not blocked by alpha4beta2 nicotinic acetylcholine receptor (nAChR) antagonists, but was partially blocked by alpha7 nAChR antagonists. Galantamine induced phosphorylation of Akt, an effector of phosphatidylinositol 3-kinase (PI3K), while PI3K inhibitors blocked the protective effect and Akt phosphorylation. The antibody FK1, which selectively blocks the allosterically potentiating ligand site on nAChR, significantly reduced the galantamine-induced protection and Akt phosphorylation. Furthermore, suppression of alpha7 nAChR using an RNA interference technique reduced Akt phosphorylation induced by galantamine. Our data suggest that neuroprotection by galantamine is mediated, at least in part, by alpha7 nAChR-PI3K cascade.

yearjournalcountryeditionlanguage
2004-10-20Biochemical and Biophysical Research Communications
https://doi.org/10.1016/j.bbrc.2004.10.132