Department of Rehabilitation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Rehabilitation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Eur J Pharm Sci. 2021 Feb 1;157:105598. doi: 10.1016/j.ejps.2020.105598. Epub 2020 Oct 16.
Several evidences suggested that TNFRSF21 exert crucial functions in regulating neuroinflammatory effects, which had been detected in Alzheimer's Disease (AD). We performed many experiments aimed to explore the comprehensively biological functions of TNFRSF21 and its underlying mechanism in AD.
Twelve normal healthy C57BL6 mice were selected, and AD model mice (APP transgenic model Tg2576 and Tau transgenic model JNPL3) were constructed and TNFRSF21 knockdown was performed in vitro. Western blotting, Co-immunoprecipitation (Co-IP), ELISA assay, flow cytometry and immunofluorescence were performed to explore the biological functions of APP and its underlying mechanism in AD.
The expression of TNFRSF21, APP, NF-κB and MAPK8 was increased in APP transgenic model (Tg2576) and Tau transgenic model (JNPL3). The interaction between TNFRSF21 and APP was analyzed by Co-IP at protein level. Based on the results of ELISA, the levels of inflammatory cytokines TNF-α, IL-5, and IFN-γ in the Tg2576 were higher than that in the JNPL3, but hardly observed in the normal group. The increased APP and inflammatory cytokines in AD model were significantly reduced with TNFRSF21 inhibited. Tg2576 group exhibited higher apoptotic rate of neuron cell and increased number of astrocytes than those of the JNPL3 group.
Our studies revealed that APP could promote and bind with TNFRSF21 to regulate the neural inflammatory effects in AD. Inhibiting TNFRSF21 could reduce APP expression and decrease neuroinflammation, which might become potential target for treating AD.
有几项证据表明，TNFRSF21 在调节神经炎症效应方面发挥着关键作用，而这种作用在阿尔茨海默病（AD）中已经得到了检测。我们进行了许多实验，旨在探索 TNFRSF21 的全面生物学功能及其在 AD 中的潜在机制。
选取 12 只正常健康的 C57BL6 小鼠，构建 AD 模型小鼠（APP 转基因模型 Tg2576 和 Tau 转基因模型 JNPL3），并在体外进行 TNFRSF21 敲低。采用 Western blot、免疫共沉淀（Co-IP）、ELISA 检测、流式细胞术和免疫荧光等方法，探讨 APP 在 AD 中的生物学功能及其潜在机制。
TNFRSF21、APP、NF-κB 和 MAPK8 的表达在 APP 转基因模型（Tg2576）和 Tau 转基因模型（JNPL3）中增加。通过 Co-IP 在蛋白质水平上分析 TNFRSF21 与 APP 的相互作用。根据 ELISA 的结果，Tg2576 中的炎症细胞因子 TNF-α、IL-5 和 IFN-γ水平高于 JNPL3，但在正常组中几乎观察不到。AD 模型中 TNFRSF21 抑制后，APP 和炎症细胞因子明显减少。Tg2576 组神经元细胞凋亡率高于 JNPL3 组，星形胶质细胞数量增加。
我们的研究表明，APP 可以促进与 TNFRSF21 的结合，从而调节 AD 中的神经炎症效应。抑制 TNFRSF21 可以减少 APP 的表达并降低神经炎症，这可能成为治疗 AD 的潜在靶点。
