In previous research, it is found that activated ATF4 induce macrophages polarized to M1 phenotype which overexpress TLR4 [26, 27]; here, by constructing PD mouse model, we found increased TLR4 in STR of PD mice, TLR4/NF-κB pathway was surprisingly attenuated in ATF4 silenced BV2 cells treated with MPP+, accompanied by decreased IL-17A and COX-2, indicating that ATF4 promoted microglia-mediated neuroinflammation through activating TLR4/NF-kB pathway. This evidence concerns the gene PTGS2 and Parkinson disease.