Department of Neurology, Fourth Hospital and Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
Department of Ophthalmology, Fourth Hospital and Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
Neurosci Lett. 2023 May 14;805:137223. doi: 10.1016/j.neulet.2023.137223. Epub 2023 Apr 3.
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.
本研究旨在探讨肿瘤坏死因子 α 诱导蛋白 3（TNFAIP3）在帕金森病（PD）发病机制中的作用及其与自噬和炎症反应的关系。PD 患者 SN 中（GSE54282 数据集）和小鼠以及 MPP 处理的 SK-N-SH 细胞中 TNFAIP3 减少。TNFAIP3 抑制炎症反应并增强自噬，从而减轻小鼠 PD。PD 小鼠 SN 和 MPP 处理的细胞中 NFκB 和 mTOR 通路被激活。TNFAIP3 通过阻止 p65 核易位和稳定 mTOR 的内源性抑制剂 DEPTOR 来阻断这两条通路。NFκB 激活剂 LPS 和 mTOR 激活剂 MHY1485 逆转了 TNFAIP3 对 MPTP 诱导的小鼠和 MPP 诱导的 SK-N-SH 细胞损伤缓解作用。总之，TNFAIP3 通过限制 NFκB 和 mTOR 通路在 MPTP 诱导的小鼠中发挥神经保护作用。
