The Effect of Genistein on the Content and Activity of α- and β-Secretase and Protein Kinase C in Aβ-Injured Hippocampal Neurons

Genistein (Gen), a derivative of soy isoflavone aglycone, has been shown to exert significant protective effect on A-induced neurotoxicity and neuroinjury. However, its underlying mechanism remains elusive. The objective was to investigate the inhibitory effect of Gen on A-induced neurotoxicity and to elucidate the underlying mechanism. Primary rat hippocampal neurons were pre-treated with Gen for 2hr followed by incubation with A 2535 for an additional 24hr. The cell viability was assessed by MTT assay. The content and activity of -, -secretase and protein kinase C (PKC) were measured, and the antagonistic effect of PKC inhibitor Myr was also analysed to clarify the molecular mechanism of Gen inhibition of A-induced toxicity to hippocampal neurons. The results showed that pre-treatment with Gen significantly increased the cell viability and presented the best effect at the final concentration of 0.375 mu g/mL. Gen increases the activity of -secretase but down-regulates the -secretase activity. It also enhances the expression and activity of PKC. Myr, a PKC inhibitor, partially blocks the activation effect of Gen. Gen exerts protective effect on A-induced neurotoxicity via activating the PKC signalling pathway, which further regulates the activities of - and -secretase and thereby inhibits the formation and toxicity of A.