To explore the roles of these pathways, we utilized Akt inhibitor and ERK inhibitor to block irisin-induced pathway activation and selected suitable doses of inhibitors, which effectively inhibited irisin-induced recovery of Akt and ERK1/2 pathways in PD models induced by neurotoxins (Supplementary Fig. 4e–h) but did not disturb the cell viability and ROS level of SH-SY5Y cells (Supplementary Fig. 4a–d). This evidence concerns the gene MAPK3 and Parkinson disease.