Edaravone-Dexborneol slows down pathological progression and cognitive decline via inhibiting S100A9 in APPswe/PS1dE9 mice
- Alzheimers Res Ther. 2025 Jun 21;17(1):139. doi: 10.1186/s13195-025-01777-9.
- 1. Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
- 2. Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China.
- 3. Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008, China.
- 4. Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210008, China.
- 5. Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. [email protected].
- 6. Jiangsu Key Laboratory for Molecular Medicine, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, China. [email protected].
- 7. Nanjing Neurology Clinical Medical Center, Nanjing Gulou Hospital Brain Disease and Brain Science Center, Nanjing, 210008, China. [email protected].
- 8. Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China. [email protected].
- 9. Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008, China. [email protected].
- 10. Nanjing Drum Tower Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Nanjing, 210008, China. [email protected].
- 11. Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China. [email protected].
- 12. Jiangsu Key Laboratory for Molecular Medicine, Institute of Translational Medicine for Brain Critical Diseases, Nanjing University, Nanjing, 210008, China. [email protected].
- 13. Nanjing Neurology Clinical Medical Center, Nanjing Gulou Hospital Brain Disease and Brain Science Center, Nanjing, 210008, China. [email protected].
- 14. Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, 210008, China. [email protected].
- # Contributed equally.
Background: Edaravone-Dexborneol (EDB) presents therapeutic effects due to its anti-inflammatory, antioxidant and anti-apoptotic properties, and has been widely used in ischemic stroke. However, the detailed efficacy and potential target of EDB in Alzheimer's disease (AD) are still elusive.
Methods: Male APPswe/PS1dE9 mice were administered with EDB intraperitoneally from 3.5 to 8 months of age. The cognition of mice was assessed by behavioral tests. Synaptic alternations in the hippocampus were detected by electrophysiology and Golgi staining. β-amyloid (Aβ) pathology was mainly observed by immunofluorescence. Oxidative stress-related indicators were evaluated by dedicated kits, while quantitative PCR and ELISA were used to detect pro-inflammatory factors. Proteomics analysis further identified the potential target of EDB.
Results: EDB was capable of delaying the cognitive decline and ameliorating the synaptic loss in APPswe/PS1dE9 mice. In addition to the anti-inflammation and anti-oxidation effects, EDB treatment mightily ablated the Aβ plaque by promoting microglial phagocytosis. Particularly, we first discovered that EDB could directly bind to S100A9, a pathological molecule that aggravates Aβ pathology and induces oxidative stress and neuroinflammation. EDB inhibited the expression, functional threonine phosphorylation and self-assembly of S100A9.
Conclusion: Our results indicate that EDB can improve cognitive function and slow down AD progression, and it may serve as a potential agent for AD and Other S100A9-related diseases.
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