| First Author | Zheng J | Year | 2021 |
| Journal | Mol Metab | Volume | 47 |
| Pages | 101180 | PubMed ID | 33556642 |
| Mgi Jnum | J:348156 | Mgi Id | MGI:6714699 |
| Doi | 10.1016/j.molmet.2021.101180 | Citation | Zheng J, et al. (2021) GLP-1 improves the supportive ability of astrocytes to neurons by promoting aerobic glycolysis in Alzheimer's disease. Mol Metab 47:101180 |
| abstractText | OBJECTIVE: Astrocytes actively participate in energy metabolism in the brain, and astrocytic aerobic glycolysis disorder is associated with the pathology of Alzheimer's disease (AD). GLP-1 has been shown to improve cognition in AD; however, the mechanism remains unclear. The objectives of this study were to assess GLP-1's glycolytic regulation effects in AD and reveal its neuroprotective mechanisms. METHODS: The Morris water maze test was used to evaluate the effects of liraglutide (an analog of GLP-1) on the cognition of 4-month-old 5xFAD mice, and a proteomic analysis and Western blotting were used to assess the proteomic profile changes. We constructed an astrocytic model of AD by treating primary astrocytes with Abeta1-42. The levels of NAD+ and lactate were examined, and the oxidative levels were assessed by a Seahorse examination. Astrocyte-neuron co-culture was performed to evaluate the effects of GLP-1 on astrocytes' neuronal support. RESULTS: GLP-1 improved cognition in 4-month-old 5xFAD mice by enhancing aerobic glycolysis and reducing oxidative phosphorylation (OXPHOS) levels and oxidative stress in the brain. GLP-1 also alleviated Abeta-induced glycolysis declines in astrocytes, which resulted in reduced OXPHOS levels and reactive oxygen species (ROS) production. The mechanism involved the activation of the PI3K/Akt pathway by GLP-1. Elevation in astrocytic glycolysis improved astrocyte cells' support of neurons and promoted neuronal survival and axon growth. CONCLUSIONS: Taken together, we revealed GLP-1's capacity to regulate astrocytic glycolysis, providing mechanistic insight into one of its neuroprotective roles in AD and support for the feasibility of energy regulation treatments for AD. |
