Ngf Regulates Expression Of Ide Through Pparγ And Pi3kin Pc12 And Neurons

Nerve growth factor (NGF) has been demonstrated to protect against Alzheimer's disease (AD) which is characterized by excessive deposition of amyloid in brain. On the other hand, insulin degrading enzyme (IDE) is responsible for process of degrading Aβ. The both are critical for the pathology of Alzeimer's disease. However, little is known about how the expression of IDE and signal pathway of NGF. Here, we show that treatment with NGF make PC12 cells grow more neurite outgrowths, treatment of hippocampal neurons and PC12 cells with NGF significantly induced expression of insulin-degrading enzyme (IDE). Furthermore, pre-treatment with an inhibitor of phosphatidylinositol 3-kinase (PI3K) markedly attenuated NGF-induced IDE expression. Finally we found expression of IDE by NGF was blocked by inhibitors of PPARγ.Our study indicates that NGF can up-regulate expression of IDE in PC12 and hippocampus neurons through PI3K and PPARγ. These data suggest a positive effect of NGF pathway on IDE expression, which may account for the protective function of NGF in AD pathogenesis, may represent a therapeutic approach to AD.