GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease

• DOI: 10.1016/j.molmet.2021.101180
• Publication Date: 2021-02-07T06:08:37Z
• Authors: Jiaping Zheng; Yunzhen Xie; Lingjia Ren; Liqin Qi; Li Wu; Xiaodong Pan; Jianxing Zhou; Zhou Chen; Libin Liu
• Keywords: Anaerobic glycolysis

Astrocytes actively participate in energy metabolism the brain, and astrocytic aerobic glycolysis disorder is associated with pathology of Alzheimer's disease (AD). GLP-1 has been shown to improve cognition AD; however, mechanism remains unclear. The objectives this study were assess GLP-1's glycolytic regulation effects AD reveal its neuroprotective mechanisms. Morris water maze test was used evaluate liraglutide (an analog GLP-1) on 4-month-old 5×FAD mice, a proteomic analysis Western blotting profile changes. We constructed an model by treating primary astrocytes Aβ1-42. levels NAD+ lactate examined, oxidative assessed Seahorse examination. Astrocyte-neuron co-culture performed astrocytes' neuronal support. improved mice enhancing reducing phosphorylation (OXPHOS) stress brain. also alleviated Aβ-induced declines astrocytes, which resulted reduced OXPHOS reactive oxygen species (ROS) production. involved activation PI3K/Akt pathway GLP-1. Elevation astrocyte cells' support neurons promoted survival axon growth. Taken together, we revealed capacity regulate glycolysis, providing mechanistic insight into one roles for feasibility treatments AD.