Effect of cx-DHED on Abnormal Glucose Transporter Expression Induced by AD Pathologies in the 5xFAD Mouse Model.

Abstract

Alzheimer's disease (AD) is a form of dementia associated with abnormal glucose metabolism resulting from amyloid-beta (Aβ) plaques and intracellular neurofibrillary tau protein tangles. In a previous study, we confirmed that carboxy-dehydroevodiamine∙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 Aβ 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-3β 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.

• Authors: Jinho Kim, ShinWoo Kang, Keun-A Chang
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 18 (Sep 13 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36142509 (Publication Type: Journal Article)

Chemical References

• Amyloid beta-Peptides
• Androstenediols
• Glucose Transport Proteins, Facilitative
• tau Proteins
• 3,16-dihydroxyandrost-5-ene-17,19-dione
• Glycogen Synthase Kinase 3 beta
• Glucose

Topics

• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Androstenediols
• Animals
• Disease Models, Animal
• Glucose (therapeutic use)
• Glucose Transport Proteins, Facilitative (genetics)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Mice
• Mice, Transgenic
• Plaque, Amyloid
• tau Proteins (metabolism)