Conclusions
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.
Methods
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.
Results
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. Conclusions: 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.