Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China; Beijing Institute of Hepatology, Beijing Key Laboratory for HIV/AIDS Research, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Neurochem Int. 2023 Dec;171:105639. doi: 10.1016/j.neuint.2023.105639. Epub 2023 Nov 3.
Neuroinflammation is an inflammatory cascade involved in various neurological disorders, including Alzheimer's disease, multiple sclerosis, and other relevant diseases. The triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane immune receptor that is primarily expressed by microglia in the central nervous system (CNS). While TREM2 is initially believed to be an anti-inflammatory factor in the CNS, increasing evidence suggests that TREM2 plays a more complex role in balancing neuroinflammation. However, the exact mechanism remains unclear. Notably, TREM2 directly regulates microglia inflammation through various signaling pathways. Additionally, studies have suggested that TREM2 mediates microglial phagocytosis, autophagy, metabolism, and microglia phenotypes, which may be involved in the modulation of neuroinflammation. In this review, we aim to discuss the critical role of TREM2 in several microglia functions and the underlying molecular mechanism the modulatory which further mediate neuroinflammation, and elaborate. Finally, we discuss the potential of TREM2 as a therapeutic target in neuroinflammatory disorders.
神经炎症是一种涉及多种神经疾病的炎症级联反应，包括阿尔茨海默病、多发性硬化症和其他相关疾病。髓样细胞触发受体 2（TREM2）是一种跨膜免疫受体，主要由中枢神经系统（CNS）中的小胶质细胞表达。虽然最初认为 TREM2 是 CNS 中的抗炎因子，但越来越多的证据表明，TREM2 在平衡神经炎症方面发挥着更复杂的作用。然而，确切的机制尚不清楚。值得注意的是，TREM2 通过各种信号通路直接调节小胶质细胞炎症。此外，研究表明，TREM2 介导小胶质细胞吞噬作用、自噬、代谢和小胶质细胞表型，这可能参与了神经炎症的调节。在这篇综述中，我们旨在讨论 TREM2 在几种小胶质细胞功能中的关键作用及其潜在的分子机制，以及进一步调节神经炎症的作用机制。最后，我们讨论了 TREM2 作为神经炎症性疾病治疗靶点的潜力。
