Knockdown of TRB3 improved the MPP+/MPTP-induced Parkinson’s disease through the MAPK and AKT signaling pathways

Abstract This study aims to investigate the function and molecular mechanisms of Tribbles homolog 3 (TRB3) on the MPP + /MPTP-induced Parkinson’s disease (PD). In this study, MPP + -induced PD cellular model and MPTP-caused PD mice model were established. Following the transfection with TRB3-shRNA, cell viability, cell apoptosis, ROS level, and the ratio of p-p38/ p38, p-JNK/JNK, p-AKT/AKT were examined. At the same time, behavior assessment of wild type female C57BL/6 mice and whole-body TRB3 knockout mice PD models caused by MPTP were performed by Rotarod test and Open-field test. The results showed that TRB3 was markedly upregulated in MPP + -induced cellular model through ATF4/CHOP pathway. Knockdown of TRB3 significantly decreased the MPP + -induced reduction of cell viability, augment of cell apoptosis and accumulation of ROS, inhibited the phosphorylation of p38 and JNK, and promoted the phosphorylation of AKT, in vitro . Further, knockout of TRB3 improved the behavior impairment of PD mice induced by MPTP, in vivo . In conclusion, knockdown of TRB3 has a neuroprotective effect on MPTP/MPP + -induced PD cellular and mice models, through regulating MAPK and AKT signaling pathways.