PI3K/AKT/FOXO信号通路介导的自噬在糖尿病认知功能障碍中的作用

糖尿病作为一种高血糖为主要特征的代谢性疾病,会引起中枢神经系统损伤,造成脑组织结构和功能改变,进而导致认知功能障碍.目前,糖尿病对认知功能障碍的影响及相关调控机制已成为国内外研究的热点和难点.磷酸肌醇3激酶/蛋白激酶B/叉头样转录因子(PI3 K/AKT/FOXO)通路是自噬的重要上游调控机制.本文概述了PI3 K/A...

The Role of PI3K/AKT/FOXO Signaling Pathway-Mediated Autophagy in Diabetes-Associated Cognitive Dysfunction

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.