Clinical study also reported that both expression of HMGB1 and TLR4 was remarkably up-regulated in PD patients compared with healthy controls, together with that the activation of NF-κB pathway and TNF-α level were positively correlated with high expression of the HMGB1/TLR4 axis (Yang et al., 2018). Here, TLR4 is linked to Parkinson disease.