Galantamine inhibits calpain-calcineurin signaling activated by beta-amyloid in human neuroblastoma SH-SY5Y cells

Galantamine, which is currently used in the treatment of patients with Alzheimer's disease (AD), has been shown to have a neuroprotective effect against beta-amyloid (Aβ) peptide-induced toxicity, which is involved in the pathogenesis of AD. In this study, we investigated the mechanism underlying the protective effect of galantamine on Aβ-induced toxicity in human neuroblastoma cells (SH-SY5Y). Using MTT and LDH leakage assays, we observed that galantamine pretreatment significantly prevented Aβ1-40-induced cell death. Aβ1-40-induced overexpression and increased cleavage of both calpain and calcineurin were observed by Western blotting and double immunofluorescent staining. Increased calcineurin phosphatase activity and decreased level of pSer112 BAD were also observed in Aβ1-40-damaged cells. However, all these alterations were found to be reversed by galantamine pretreatment. We also found that the neuroprotection of galantamine can be blocked by an α7 nAChR antagonist. Overall, our results suggest that galantamine may prevent the neuronal damage induced by Aβ1-40 through a mechanism related to the regulation of calpain-calcineurin activation and BAD phosphorylation, which may involve the participation of α7 nAChR.