PSD-93 mediates the crosstalk between neuron and microglia and facilitates acute ischemic stroke injury by binding to CX3CL1.
J Neurochem
; 157(6): 2145-2157, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33599284
ABSTRACT
Post-synaptic 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 post-synaptic 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 examined the interaction of PSD-93 and CX3CL1 in the crosstalk between neurons and microglia in acute ischemic stroke. We utilized male C57BL/6 mice to establish the middle cerebral artery occlusion model (MCAO) and designed a fusion small peptide Tat-CX3CL1 (357-395aa) to inhibit PSD-93 and CX3CL1 interaction. The combination peaks of PSD-93 and CX3CL1 at 6 hr after I/R were observed. The binding sites were located at 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-1ß and TNF-α expression and provided neuroprotection following reperfusion. Together, these data suggest that 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
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Microglia
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Guanilato Quinases
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Quimiocina CX3CL1
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AVC Isquêmico
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Proteínas de Membrana
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Neurônios
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China