Genistein protects against rat hippocampus amyloid-β 1-42 neurotoxicity through p-mTOR-dependent autophagy

Deposition of amyloid beta (Aβ) protein is a biomarker of severe Alzheimer’s disease (AD), and leads to neural dysfunction and cell function disorders. Genistein (Gen) may exert a significant protective effect against Aβinduced neurotoxicity, but the underlying mechanism remains elusive. Thus, this study aimed to explore the regulatory mechanism of Gen. Cell viability was evaluated using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Moreover, apoptosis was analyzed using flow cytometry. The effect of Gen or MHY1485, an activator of the mammalian target of rapamycin (mTOR), on autophagosome formation was observed through transmission electron microscopy. In addition, phosphorylated (p)-mTOR, microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine conjugate (LC3-II), and beclin 1 expression levels were detected via western blotting analysis. Gen significantly increased cell survival rate, which was deceased by Aβ1-42 pretreatment, and decreased the apoptosis induced by Aβ1-42 pretreatment. In addition, Gen reduced Aβ1-42-induced excessive autophagy. Moreover, Gen treatment reduced autophagic vesicle formation, conversion of LC3-I to LC3-II, and beclin 1 expression, which were all increased by Aβ1-42 pretreatment in the neurons. Additionally, Gen markedly suppressed the level of p-mTOR, which was upregulated by Aβ1-42 treatment. Finally, the p-mTOR-specific activator MHY1485 weakened the effect of Gen on cell survival, cell apoptosis, and cell autophagy induced by Aβ1-42 treatment. Taken together, these results suggested that Gen protects hippocampal neurons against Aβ1-42 induced neurotoxicity in rats by decreasing the level of p-mTOR, thus attenuating apoptosis and p-mTOR-dependent autophagy. These findings offer novel insights into the signaling pathway involved in Aβ1-42 toxicity, and the neuroprotective action of Gen.