Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
J Neuroinflammation. 2020 Jul 7;17(1):204. doi: 10.1186/s12974-020-01878-2.
Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor mainly expressed on the surface of microglia. It mediates multiple pathophysiological processes in various diseases. Recently, TREM2 has been found to play a role in the development of Alzheimer's disease (AD). TREM2 is a transmembrane protein that is specifically expressed on microglia in the brain. It contains a long ectodomain that directly interacts with the extracellular environment to regulate microglial function. The ectodomain of TREM2 is processed by a disintegrin and metalloprotease, resulting in the release of a soluble form of TREM2 (sTREM2). Recent studies have demonstrated that sTREM2 is a bioactive molecule capable of binding ligands, activating microglia, and regulating immune responses during the AD continuum. Clinical studies revealed that sTREM2 level is elevated in cerebrospinal fluid (CSF) of AD patients, and the sTREM2 level is positively correlated with the levels of classical CSF biomarkers, namely t-tau and p-tau, indicating that it is a reliable predictor of the early stages of AD. Herein, we summarize the key results on the generation, structure, and function of sTREM2 to provide new insights into TREM2-related mechanisms underlying AD pathogenesis and to promote the development of TREM2-based therapeutic strategy.
髓系细胞触发受体 2（TREM2）是一种主要表达在小胶质细胞表面的受体，它介导多种疾病中的多种病理生理过程。最近，发现 TREM2 在阿尔茨海默病（AD）的发展中起作用。TREM2 是一种跨膜蛋白，在大脑中的小胶质细胞上特异性表达。它包含一个长的细胞外结构域，直接与细胞外环境相互作用，调节小胶质细胞的功能。TREM2 的细胞外结构域通过一种解整合素和金属蛋白酶进行处理，导致 TREM2 的可溶性形式（sTREM2）的释放。最近的研究表明，sTREM2 是一种具有生物活性的分子，能够结合配体，激活小胶质细胞，并在 AD 连续体中调节免疫反应。临床研究表明，AD 患者脑脊液（CSF）中的 sTREM2 水平升高，并且 sTREM2 水平与经典 CSF 生物标志物 t-tau 和 p-tau 的水平呈正相关，表明它是 AD 早期阶段的可靠预测因子。在此，我们总结了关于 sTREM2 的产生、结构和功能的关键结果，为 TREM2 相关机制在 AD 发病机制中的作用提供了新的见解，并促进了基于 TREM2 的治疗策略的发展。
