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

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.