Effects Of 17β-estradiol On Creb Phosphorylation In Pc12 Cells Treated With Sublethal Aβ_1-42

It is widely accepted that cAMP response element binding protein (CREB) is the core component in the process of learning and memory which is undermined in patients of Alzheimer's Disease (AD). Besides, epidemiological investigation indicates the declining memory is correlated with the lower estrogen level in AD patients. However, the effect of estrogen on CREB activity in AD is poorly known. In this study, we investigated the effect of 17β-estradiol pretreatment on the phosphorylation level of both CREB and the kinases associated with CREB activation in cells exposed to a sublethal concentration of Aβ1-42. We found that 17β-estradiol pretreatment prevented Aβ1-42 induced down-regulation of CREB phosphorylation. Furthermore, significant increases in phosphorylation of both Protein kinase B (Akt) and glycogen synthase kinase-3β(GSK-3β) were detected in sublethal Aβ1-42 treated cells with pretreatment of 17β-estradiol, suggesting the activation of Akt and inactivation of GSK-3βmay be involved in the mechanism underlying the neuroprotection provided by 17β-estradiol pretreatment.