BACKGROUND The mechanisms underlying the pathogenesis and progression of Parkinson's disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration in A53T mice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia. METHODS After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 in A53T mice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation. RESULTS We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia of A53T mice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation. CONCLUSIONS Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.

中文翻译：

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CXCL12参与帕金森氏病的α-突触核蛋白触发的神经炎症。

背景技术帕金森氏病（PD）的发病机理和进展的机制尚不清楚，但是最近的观点和观点集中在由小胶质细胞诱导的炎症过程是否有助于α-突触核蛋白介导的毒性。小胶质细胞向黑质（SN）的迁移可能先于A53T小鼠的神经变性。我们假设CXCL12可能是α-突触核蛋白诱导的小胶质细胞迁移的介体。方法建立适当的动物和细胞培养模型后，我们探讨了A53T小鼠，原发性小胶质细胞和BV-2细胞系中α-突触核蛋白与CXCL12之间的关系。我们还探讨了这些相互作用的机制和神经炎症涉及的信号传导过程。结果我们证实了PD患者死后脑组织中α-突触核蛋白和CXCL12与A53T小鼠SN小胶质细胞中CXCR4表达上调呈正相关。此外，正如预期的那样，α-突触核蛋白通过TLR4 /IκB-α/NF-κB信号传导增加了小胶质细胞中CXCL12的产生。重要的是，CXCL12 / CXCR4 / FAK / Src / Rac1信号显示参与α-突触核蛋白诱导的小胶质细胞积聚。结论我们的研究表明CXCL12可能是预防α-突触核蛋白触发的持续性小胶质细胞反应的新靶标。阻断CXCL12 / CXCR4可能是PD进展的潜在治疗方法。α-突触核蛋白通过TLR4 /IκB-α/NF-κB信号传导增加小胶质细胞CXCL12的产生。重要的是，CXCL12 / CXCR4 / FAK / Src / Rac1信号显示参与α-突触核蛋白诱导的小胶质细胞积聚。结论我们的研究表明CXCL12可能是预防α-突触核蛋白触发的持续性小胶质细胞反应的新靶标。阻断CXCL12 / CXCR4可能是PD进展的潜在治疗方法。α-突触核蛋白通过TLR4 /IκB-α/NF-κB信号传导增加小胶质细胞CXCL12的产生。重要的是，CXCL12 / CXCR4 / FAK / Src / Rac1信号显示参与α-突触核蛋白诱导的小胶质细胞积聚。结论我们的研究表明CXCL12可能是预防α-突触核蛋白触发的持续性小胶质细胞反应的新靶标。阻断CXCL12 / CXCR4可能是PD进展的潜在治疗方法。