Transmissible spongiform encephalopathies (TSEs) are epidemic neurodegenerative diseases caused by prion proteins; in particular, they are induced by misfolded prion proteins (PrP^Sc). PrP^Sc tend to aggregate into insoluble amyloid prion fibrils (fPrP^WT), resulting in apoptosis of neuron cells and sequential neurodegeneration. Previous studies indicate that microglia cells play an important role in the innate immune system, and that these cells have good neuroprotection and delay the onset of TSEs. However, microglia can be a double-sided blade. For example, both Cu²⁺ and Mn²⁺ can induce microglia activation and secrete many inflammatory cytokines that are fatal to neuron cells. Unfortunately, PrP have cation binding sites at the N-terminus. When PrP^Sc accumulate during microglial phagocytosis, microglia may change the phenotype to secrete pro-inflammation cytokines, which increases the severity of the disease. Some studies have revealed an increase in the concentration of Mn²⁺ in the brains of patients. In this study, we treated microglia with fPrP^WT and cations and determined IκBα and IL-1β expression by Western blotting and quantitative polymerase chain reaction. The results showed that Mn–fPrP^WT decreased IκBα levels and dramatically increased IL-1β mRNA expression. In addition, competing binding between Cu²⁺ and Mn²⁺ can decrease the effect of Mn–fPrP^WT on IκBα and IL-1β. The effects of divalent cations and fPrP^WT in microglia inflammation are also discussed.

中文翻译：

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二价阳离子螯合朊病毒原纤维对 EOC 13.31 小胶质细胞免疫反应的影响


传染性海绵状脑病 (TSE) 是由朊病毒蛋白引起的流行性神经退行性疾病；特别是，它们是由错误折叠的朊病毒蛋白（PrP ^Sc ）诱导的。 PrP ^Sc倾向于聚集成不溶性淀粉样蛋白朊病毒原纤维 (fPrP ^WT )，导致神经元细胞凋亡和后续神经变性。此前的研究表明，小胶质细胞在先天免疫系统中发挥着重要作用，并且这些细胞具有良好的神经保护作用，可以延缓 TSE 的发生。然而，小胶质细胞可以是双面刀片。例如，Cu ²⁺和Mn ²⁺都可以诱导小胶质细胞活化并分泌许多对神经元细胞致命的炎症细胞因子。不幸的是，PrP 在 N 末端有阳离子结合位点。当小胶质细胞吞噬过程中 PrP ^Sc积累时，小胶质细胞可能会改变表型，分泌促炎细胞因子，从而增加疾病的严重程度。一些研究表明，患者大脑中 Mn ²⁺的浓度有所增加。在本研究中，我们用 fPrP ^WT和阳离子处理小胶质细胞，并通过蛋白质印迹和定量聚合酶链反应测定 IκBα 和 IL-1β 的表达。结果表明，Mn-fPrP ^WT降低了 IκBα 水平，并显着增加了 IL-1β mRNA 表达。此外，Cu ²⁺和Mn ²⁺之间的竞争结合可以降低Mn-fPrP ^WT对IκBα 和IL-1β 的影响。还讨论了二价阳离子和 fPrP ^WT在小胶质细胞炎症中的作用。