Salidroside attenuates hypoxia-induced abnormal processing of amyloid precursor protein by decreasing BACE1 expression in SH-SY5Y cells.

Hypoxia which is mainly mediated by hypoxia-inducible factor 1 (HIF-1), can greatly contribute to the occurrence of Alzheimer's disease (AD) by increasing beta-site APP cleaving enzyme (BACE1) gene expression, protein level and beta-secretase activity, resulting in a significant generation of amyloid-beta (Abeta). Salidroside has been reported to have great neuroprotective effects. The aim of this study was to investigate the effects of salidroside on hypoxia-induced abnormal processing of the amyloid precursor protein (APP) in SH-SY5Y cells and its possible mechanism. Western blot analysis showed that 200muM of salidroside pretreatment significantly decreased BACE1 protein level and promoted the secretion of sAPPalpha in hypoxic condition. Salidroside had no effect on the level of APP, ADAM10 and ADAM17. ELISA analysis revealed that salidroside was able to inhibit the increase of beta-secretase activity and Abeta generation induced by hypoxia, with no effect on gamma-secretase activity. Notably, under hypoxia condition, mRNA of BACE1 and protein level of HIF-1alpha were decreased by salidroside pretreatment. These results demonstrated for the first time that salidroside was able to attenuate abnormal processing of amyloid precursor protein induced by hypoxia in SH-SY5Y cells, providing a new insight into prevention and treatment of Alzheimer's disease.