Effect of cx-DHED on Abnormal Glucose Transporter Expression Induced by AD Pathologies in the 5xFAD Mouse Modelopen access
- Authors
- Kim, Jinho; Kang, ShinWoo; Chang, Keun-A
- Issue Date
- Sep-2022
- Publisher
- MDPI
- Keywords
- cx-DHED; Alzheimer' s disease; glucose transport; GSK-3 beta; O-GlcNac
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.23, no.18
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 23
- Number
- 18
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/85886
- DOI
- 10.3390/ijms231810602
- ISSN
- 1661-6596
- Abstract
- Alzheimer's disease (AD) is a form of dementia associated with abnormal glucose metabolism resulting from amyloid-beta (A beta) plaques and intracellular neurofibrillary tau protein tangles. In a previous study, we confirmed that carboxy-dehydroevodiamine center dot HCl (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 A beta 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-3 beta 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.
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