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• W4253190479 abstract "Abstract Background: Postsynaptic density 93 (PSD-93) mediates glutamate excitotoxicity induced by ischemic brain injury, which then induces microglial inflammatory response. However, the underlying mechanisms of how PSD-93 mediates the crosstalk between neurons and microglia in the postsynaptic dense region remain elusive. CX3 chemokine ligand 1 (CX3CL1) is a chemokine specifically expressed in neurons while its receptor CX3CR1 is highly expressed in microglia. In this study, we aimed to investigate the role of PSD-93 and CX3CL1 interaction in the crosstalk between neuron and microglia in acute ischemic stroke. Methods: Male C57BL/6 mice were used to establish middle cerebral artery occlusion model and co-immunoprecipitation and immunoblotting were used to detect the binding of PSD-93 and CX3CL1 at different time points following cerebral ischemic/reperfusion (I/R). ELISA was used to detect soluble CX3CL1. Yeast two-hybrid and co-immunoprecipitation were used to identify special amino acid sequences responsible for the interaction between PSD-93 and CX3CL1. Finally, a fusion small peptide Tat-CX3CL1 was designed to inhibit PSD-93 and CX3CL1 interaction. Results: The binding of PSD-93 and CX3CL1 peaked at 6 h after I/R. The binding sites were located in the 420-535 amino acid sequence of PSD-93 and 357-395 amino acid sequence of CX3CL1. Tat-CX3CL1 (357-395aa) could inhibit the interaction of PSD-93 and CX3CL1 and inhibited the pro-inflammatory cytokine IL-1β and TNF-α expression and provided neuroprotection following reperfusion. Conclusions: PSD-93 binds CX3CL1 to activate microglia and initiate neuroinflammation. Specific blockade of PSD-93-CX3CL1 interaction reduces I/R induced neuronal cell death, and provides a new therapeutic target for ischemic stroke." @default.
• W4253190479 created "2022-05-12" @default.
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• W4253190479 date "2020-05-15" @default.
• W4253190479 modified "2023-09-27" @default.
• W4253190479 title "PSD-93 mediates the crosstalk between neuron and microglia and facilitates acute ischemic stroke injury by binding to CX3CL1" @default.
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• W4253190479 doi "https://doi.org/10.21203/rs.2.20106/v2" @default.
• W4253190479 hasPublicationYear "2020" @default.
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