Triggering Receptor Expressed on Myeloid Cells 2 Protects Dopaminergic Neurons by Promoting Autophagy in the Inflammatory Pathogenesis of Parkinson's Disease.
Triggering Receptor Expressed on Myeloid Cells 2 Protects Dopaminergic Neurons by Promoting Autophagy in the Inflammatory Pathogenesis of Parkinson's Disease.
复制标题
骨髓细胞 2 上表达的触发受体通过促进帕金森病炎症发病机制中的自噬来保护多巴胺能神经元。
DOI：
10.3389/fnins.2021.745815
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发表时间：
2021
影响因子：
4.3
通讯作者：
Lu G
中科院分区：
文献类型：
--
作者：
Huang W;Lv Q;Xiao Y;Zhong Z;Hu B;Yan S;Yan Y;Zhang J;Shi T;Jiang L;Li W;Lu G
帕金森病是一种以炎症反应为核心致病机制的神经退行性疾病。以前的人类遗传学研究结果支持TREM 2功能丧失会加重神经退行性变的观点，而TREM 2是小胶质细胞中表达最高的受体之一。然而，TREM 2在PD炎症机制中的作用尚不清楚。我们的研究发现，无论是在体内还是体外，小胶质细胞的激活不仅促进了炎症因子的分泌，而且降低了TREM 2的水平，抑制了自噬的发生。相反，TREM 2水平的增加降低了炎症因子的表达，并通过p38 MAPK/mTOR途径增强了自噬水平。此外，增加TREM 2表达显著减少多巴胺能（DA）神经元的凋亡，并改善PD小鼠的运动能力。总之，TREM 2是PD发病机制和炎症之间的重要联系。我们的研究为TREM 2在PD中的作用机制提供了新的视角，并揭示了TREM 2作为PD潜在的治疗靶点。
Parkinson’s disease is a neurodegenerative disorder with an inflammatory response as the core pathogenic mechanism. Previous human genetics findings support the view that the loss of TREM2 function will aggravate neurodegeneration, and TREM2 is one of the most highly expressed receptors in microglia. However, the role of TREM2 in the inflammatory mechanism of PD is not clear. In our study, it was found both in vivo and in vitro that the activation of microglia not only promoted the secretion of inflammatory factors but also decreased the level of TREM2 and inhibited the occurrence of autophagy. In contrast, an increase in the level of TREM2 decreased the expression of inflammatory factors and enhanced the level of autophagy through the p38 MAPK/mTOR pathway. Moreover, increased TREM2 expression significantly decreased the apoptosis of dopaminergic (DA) neurons and improved the motor ability of PD mice. In summary, TREM2 is an important link between the pathogenesis of PD and inflammation. Our study provides a new view for the mechanism of TREM2 in PD and reveals TREM2 as a potential therapeutic target for PD.
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影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
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5.3
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