Study On Molecular Mechanism Of Genistein Against Beta-amyloid-induced Neurotoxicity In Hippocampal Neurons

Genistein (Genistein, Gen),wideLy found in leguminous plant, is the main comp- onent of soy isoflavone aglycone. Having a strong physiological activity and similar molecular structure with endogenous estrogen,Gen has a strong physiological activity and similar molecular structure with endogenous estrogen. In the human body, Gen can bind estrogen receptors and play a weak role in the estrogenic and anti-estrogen active, while it has some affinity with estrogen receptors. Studies show that estrogen has a significant protective effect on neuronaL cells, and it can be used for prevention and treatment of senile neurodegenerative diseases. The previous animal studies showed that isoflavone aglycone can improve AD (Alzheimer's disease, AD) model mice capabilty of learning and memory, and increase antioxidant capability, reduce cortical AchE activity to protect the neurotransmitter in AD model mice, and reduceβ-secretase activity in hippocampus of AD mice, to reduce excessive accumulation of Aβwhich caused neurotoxicity in hippocampus of mice and protect the AD mice. Gen have a good activity to prevent and treat to AD. The protection mechanism may have relevance with PKC (Protein kinase C, PKC). More disscussions about neruoprotection mechanism of Gen in cellular level will be available in this paper.To set up the AD cell model using primary hippocampal neuronaL cell induced withβ-amyloid peptide (Aβ25-35). The hippocampal neuronal cell was cultured in vitro and different concentrations Gen pre-incubated with Aβ25-35, then detct the change of cell morphology and survival rate of rat hippocampal neurons, to reserch the protective effect of Gen; and determine the changeα,β-secretase and protein kinase C(PKC) activity and PKCαcontent, and PKC inhibitor(Myristoylated Protein Kinase C Peptide Inhibitor, Myr) impact on neuroprotection. To investigate molecular mechanisms of Gen against Aβ25–35 - induced toxicity in hippocampal neurons. The results showed that, 25μmol/L Aβ25-35 can be used to build AD cell model; Gen can significantly improve cell morphology of Aβ-induced and increased cell survival, 0.375μg/mL of Gen have the greatest protective effect; Gen has raisedα-secretase activity and reducedβ-secretase activity, and increased PKC activity and the expression content of PKCα.. The activation effect of Gen couLd be partially blocked by PKC inhibitors Myr. The present study on the protective effects of Gen against Aβ25–35-induced toxicity showed that,its molecular mechanism may be through the PKC signal transduction pathway activated by Gen, thereby regulating theα,β-secretase activity, inhibiting the formation and toxicity of Aβ, and play a neuroprotective role.