Edaravone-Dexborneol slows down pathological progression and cognitive decline via inhibiting S100A9 in APPswe/PS1dE9 mice
Abstract 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....
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-025-01777-9 |
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| Summary: | Abstract 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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| ISSN: | 1758-9193 |