Knockdown of PDCD4 ameliorates neural cell apoptosis and mitochondrial injury through activating the PI3K/AKT/mTOR signal in Parkinson’s disease

Parkinson’s disease (PD) is a complex neurodegenerative disorder and hampers normal living. It has been reported that programmed cell death 4 (PDCD4) is associated with tumor suppression, inflammatory response, and apoptosis. The aim of this study was to investigate the role of PDCD4 in PD. The in vivo and in vitro PD models were established by MPTP-induced mice and MMP+ stimulated MN9D cells, respectively. The expression of PDCD4 was detected by western blot. The MN9D cell viability and apoptosis were determined by MTT and flow cytometry assay. Moreover, the MN9D cell mitochondrial injury was evaluated by JC-1 staining. In this study, PDCD4 was highly expressed in brain tissue of MPTP-induced PD mouse model. In a loss-function experiments, knockdown of PDCD4 promoted MN9D cell viability and allayed MPP+-triggered MN9D cell apoptosis. Furthermore, knockdown of PDCD4 ameliorated MPP+-evoked MN9D cell mitochondrial injury. Mechanically, knockdown of PDCD4 abolished the effect of MMP+ stimulation via activating phosphoinositide 3-kinase(PI3K)/AKT/mammalian target of rapamycin (mTOR) signal. Notably, the protective effects of shPDCD4 on cell apoptosis and mitochondrial injury were suppressed by PI3K inhibitor LY294002. In summary,knockdown of PDCD4 ameliorates neural cell apoptosis and mitochondrial injury through activating the PI3K/AKT/mTOR signal, providing a novel target for PD treatment. All data generated or analyzed during this study are included in this published article. •PDCD4 is highly expressed in MPTP-induced PD mouse model•Knockdown of PDCD4 promoted MN9D cell viability and ameliorated MPP+-evoked MN9D cell apoptosis•Knockdown of PDCD4 ameliorated MPP+-evoked MN9D cell mitochondrial injury•Knockdown of PDCD4 abolished the effect of MMP+ stimulation via activating PI3K/AKT/mTOR signal in MN9D cells•The protective effects of shPDCD4 on MN9D cell apoptosis and mitochondrial injury was performed by activating PI3K/AKT/mTOR signal