The Role of PI3K / AKT / FOXO Signaling Pathway-mediated Autophagy in Diabetes-associated Cognitive Dysfunction / 中国生物化学与分子生物学报

ABSTRACT

Diabetes‚ a metabolic disease characterized by hyperglycemia‚ can cause central nerve system damage‚ lead to alteration of the neuronal structure and function‚ and consequently induce cognitive dysfunction. Recently‚ diabetes-associated cognitive dysfunction (DACD) and its molecular mechanism have become a research frontier. The phospoinositide 3 kinase/ protein kinase B/ Forkhead box O (PI3K/ PKB/ FOXO) signaling pathway is an important upstream regulatory mechanism for autophagy. Here we review the role of the PI3K/ AKT/ FOXO signaling pathway in the regulation of Gs‚ Bnip3 and Spk2 gene expressions. GS regulates the Gln-mTORC1 pathway and thus activates autophagy; BNIP3 enhances LC3 expression and promotes autophagy. Moreover‚ the AMPK-FOXO3a-mTORC1 signaling pathway is also an important pathway that involved in the regulation of autophagy. These studies suggest that FOXO3a may be a key target for the treatment of DACD. This review aims to provide a theoretical basis and molecular target for the clinical treatment of DACD and it related drug development.