Genistein attenuates memory impairment in Alzheimer's disease via ERS-mediated apoptotic pathway in vivo and in vitro

Genistein (GS), an isoflavone compound found in soybean, plays a neuroprotective role in Alzheimer's disease (AD). However, the mechanism of its action remains unclear. Herein, binding ability between GS and GRP78 was predicted by molecular docking, and the effect of GS in vivo and vitro were further studied. In this study, the effects of GS on learning and memory ability, changes of hippocampal neurons and ultrastructure of hippocampal CA3 region in AD rats were investigated. Besides, the protein or mRNA levels of the related proteins were detected. The results showed GS could effectively improve the learning and the memory ability, reduce the damage of hippocampal neurons, and decrease the protein or mRNA expression levels of GRP78, CHOP, Caspase-12, Cle-Caspase-9, Cle-Caspase-3, PERK, and p-PERK. Taken together, our data reveal GS has a neuroprotective effect by inhibiting the ERS-mediated apoptotic pathway, which may be a new therapeutic target for the treatment of AD.