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

Genistein ( G en), a derivative of soy isoflavone aglycone, has been shown to exert significant protective effect on A β‐induced neurotoxicity and neuroinjury. However, its underlying mechanism remains elusive. The objective was to investigate the inhibitory effect of G en on A β‐induced neurotoxicity and to elucidate the underlying mechanism. Primary rat hippocampal neurons were pre‐treated with G en for 2 hr followed by incubation with A β 25–35 for an additional 24 hr. The cell viability was assessed by MTT assay. The content and activity of α‐, β‐secretase and protein kinase C ( PKC ) were measured, and the antagonistic effect of PKC inhibitor M yr was also analysed to clarify the molecular mechanism of G en inhibition of A β‐induced toxicity to hippocampal neurons. The results showed that pre‐treatment with G en significantly increased the cell viability and presented the best effect at the final concentration of 0.375 µg/mL. G en increases the activity of α‐secretase but down‐regulates the β‐secretase activity. It also enhances the expression and activity of PKC . M yr, a PKC inhibitor, partially blocks the activation effect of G en. G en exerts protective effect on A β‐induced neurotoxicity via activating the PKC signalling pathway, which further regulates the activities of α‐ and β‐secretase and thereby inhibits the formation and toxicity of A β.