Tumor necrosis factor α-induced protein 3 mediates inflammation and neuronal autophagy in Parkinson's disease via the NFκB and mTOR pathways.

This study aimed to probe the function of tumor necrosis factor α-induced protein 3 (TNFAIP3) in the pathogenesis of Parkinson disease (PD) with its association with autophagy and inflammatory response. TNFAIP3 was reduced in the SN of PD patients (the GSE54282 dataset) and mice and in the MPP-treated SK-N-SH cells. TNFAIP3 inhibited inflammatory response and enhanced autophagy, thereby alleviating PD in mice. NFκB and mTOR pathways were activated in the SN of PD mice and MPP-treated cells. TNFAIP3 blocked the two pathways by preventing the p65 nuclear translocation and stabilizing DEPTOR, an endogenous inhibitor of mTOR. NFκB activator LPS and mTOR activator MHY1485 reversed the effects of TNFAIP3 on mitigation of injury in PD mice and in SK-N-SH cells induced with MPP. Altogether, TNFAIP3 played a neuroprotective role in MPTP-induced mice by restricting NFκB and mTOR pathways.