PSD ‐93 mediates the crosstalk between neuron and microglia and facilitates acute ischemic stroke injury by binding to CX3CL1

In this study, we examined the interaction of PSD‐93 and CX3CL1 in the crosstalk between neurons and microglia in acute ischemic stroke. We utiliz ed 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‐1β and TNF‐α expression and provided neuroprotection following reperfu sion. 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.

Source: Journal of Neurochemistry - March 8, 2021 Category: Neuroscience Authors: Qingxiu Zhang, Lei He, Mo Chen, Hui Yang, Xiaowei Cao, Xiaomei Liu, Qi Hao, Zhengwei Chen, Tengfei Liu, Xiu ‐e Wei, Liangqun Rong Tags: ORIGINAL ARTICLE Source Type: research