| First Author | Kim J | Year | 2022 |
| Journal | Int J Mol Sci | Volume | 23 |
| Issue | 18 | PubMed ID | 36142509 |
| Mgi Jnum | J:329867 | Mgi Id | MGI:7342740 |
| Doi | 10.3390/ijms231810602 | Citation | Kim J, et al. (2022) Effect of cx-DHED on Abnormal Glucose Transporter Expression Induced by AD Pathologies in the 5xFAD Mouse Model. Int J Mol Sci 23(18) |
| abstractText | Alzheimer's disease (AD) is a form of dementia associated with abnormal glucose metabolism resulting from amyloid-beta (Abeta) plaques and intracellular neurofibrillary tau protein tangles. In a previous study, we confirmed that carboxy-dehydroevodiamineHCl (cx-DHED), a derivative of DHED, was effective at improving cognitive impairment and reducing phosphorylated tau levels and synaptic loss in an AD mouse model. However, the specific mechanism of action of cx-DHED is unclear. In this study, we investigated how the cx-DHED attenuates AD pathologies in the 5xFAD mouse model, focusing particularly on abnormal glucose metabolism. We analyzed behavioral changes and AD pathologies in mice after intraperitoneal injection of cx-DHED for 2 months. As expected, cx-DHED reversed memory impairment and reduced Abeta plaques and astrocyte overexpression in the brains of 5xFAD mice. Interestingly, cx-DHED reversed the abnormal expression of glucose transporters in the brains of 5xFAD mice. In addition, otherwise low O-GlcNac levels increased, and the overactivity of phosphorylated GSK-3beta decreased in the brains of cx-DHED-treated 5xFAD mice. Finally, the reduction in synaptic proteins was found to also improve by treatment with cx-DHED. Therefore, we specifically demonstrated the protective effects of cx-DHED against AD pathologies and suggest that cx-DHED may be a potential therapeutic drug for AD. |
