Department of Pharmacology & Toxicology, School of Pharmacy, The University of Kansas, Lawrence, KS 66045, USA.
Higuchi Biosciences Center, The University of Kansas, Lawrence, KS 66045, USA.
Cells. 2021 Feb 4;10(2):321. doi: 10.3390/cells10020321.
Alzheimer's disease (AD) is a lethal neurodegenerative disorder primarily affecting the aged population. The etiopathogenesis of AD, especially that of the sporadic type, remains elusive. The triggering receptor expressed on myeloid cells 2 (TREM2), a member of TREM immunoglobulin superfamily, plays a critical role in microglial physiology. Missense mutations in human are determined as genetic risk factors associated with the development of sporadic AD. However, the roles of TREM2 in the pathogenesis of AD are still to be established. In this review, we outlined the influence of Trem2 on balance of pro- and anti-inflammatory microglial activations from a perspective of AD mouse model transcriptomics. On this basis, we further speculated the roles of TREM2 in different stages of AD, which may shed light to the development of TREM2-targeted strategy for the prevention and treatment of this neurodegenerative disorder.
阿尔茨海默病(AD)是一种致命的神经退行性疾病,主要影响老年人群。AD 的病因发病机制,尤其是散发性 AD 的病因发病机制,仍然难以捉摸。髓样细胞表达的触发受体 2(TREM2)是 TREM 免疫球蛋白超家族的成员,在小胶质细胞生理学中发挥关键作用。人类 中的错义突变被确定为与散发性 AD 发展相关的遗传风险因素。然而,TREM2 在 AD 发病机制中的作用仍有待确定。在这篇综述中,我们从 AD 小鼠模型转录组学的角度概述了 Trem2 对促炎和抗炎小胶质细胞激活平衡的影响。在此基础上,我们进一步推测了 TREM2 在 AD 不同阶段的作用,这可能为开发针对 TREM2 的策略预防和治疗这种神经退行性疾病提供思路。