iProXProteomicsYun XuMus Musculushttp://www.iprox.org/page/project.html?id=IPX0009468000xuyun20042001@aliyun.comNanjing Drum Tower HospitaliProX<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Edaravone-Dexborneol slows down pathological progression and cognitive decline via inhibiting S100A9 in APPswe/PS1dE9 mice.Mao Rui R, Shu Shu S, Sun Min M, Chen Jiang J, Hu Mengsha M, Ye Lei L, Xu Siyi S, Jia Junqiu J, Shao Wenxuan W, Bao Xinyu X, Xu Yun Y, Zhu Xiaolei XfalseQuantitative proteomics of EDB-treated APP/PS1 miceHippocampal proteins were extracted from the brain tissues of APP+SA and APP+EDB mice. The proteomics experiments and subsequent bioinformatics analysis were supported by OE Biotech Co..Tue Aug 13 00:00:00 GMT+01:00 2024PXD0548451009040544243