Galantamine protects against oxidative stress induced by amyloid-beta peptide in cortical neurons.
Galantamine is currently used in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). Although its action is mostly directed at the regulation of cholinergic transmission, galantamine can also afford neuroprotection against amyloid-beta peptide (Abeta), which is involved in AD pathogenesis. In this study, we used cultured rat cortical neurons treated with two forms of Abeta(1-40), fresh and previously aged (enriched in fibrils). First, we confirmed that galantamine prevented neurodegeneration induced by both peptide forms in a concentration-dependent manner. Moreover, we observed that when neurons were co-incubated with fresh Abeta(1-40) plus galantamine, the amount of amyloid aggregates was reduced. As oxidative conditions influence Abeta aggregation, we investigated whether galantamine prevents oxidative stress induced by this peptide. The data show that either fresh or aged Abeta(1-40) significantly increased the amount of reactive oxygen species and lipoperoxidation, these effects being prevented by galantamine. In Abeta(1-40)-treated neurons, the depletion of reduced glutathione (GSH) seems to be related to the decrease in glutathione peroxidase and glutathione reductase activities(.) These alterations in the GSH antioxidant system were prevented by galantamine. Overall, these results constitute the first evidence that galantamine can prevent the neuronal oxidative damage induced by Abeta, providing an in vitro basis for the beneficial actions of galantamine in the AD neurodegenerative process.
Melo
Joana B
JB
Center for Neurosciences and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Sousa
Carla
C
Garção
Pedro
P
Oliveira
Catarina R
CR
Agostinho
Paula
P
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005702:Galantamine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D005702:Galantamine; D005978:Glutathione