Laboratory of Endocrinology and Genomics, CHUQ (CHUL) Research Center and Department of Molecular Medicine, Faculty of Medicine, Laval University, 2705 Laurier boul., Québec, Canada G1V 4G2.
Stem Cell Rev Rep. 2012 Sep;8(3):898-904. doi: 10.1007/s12015-012-9356-9.
Accumulating evidence supports a critical role of Toll-like receptors in the clearance of Amyloid beta (Aβ) by microglial cells. Myeloid differentiation factor 88 (MyD88) is an adaptor protein that bridges the intracellular signal to nucleus for most of these innate immune receptors. We investigated here the role of competent MyD88 hematopoietic stem cells on the cognitive decline of a mouse model of Alzheimer's disease (AD). We generated classical chimeric mouse models using irradiation and transplantation of wild type GFP cells and MyD88-deficient cells. Transplantation of GFP cells essentially rescued the cognitive impairment, whereas MyD88-deficient cells significantly accelerated memory deficits of APP(swe)/PS1 mice. Moreover, we found that monocytes and microglia deficient for MyD88 exhibit a functionally impaired phagocytic reaction to Aβ.
越来越多的证据表明 Toll 样受体在小胶质细胞清除淀粉样β（Aβ）中起着关键作用。髓样分化因子 88（MyD88）是一种衔接蛋白，它为大多数先天免疫受体将细胞内信号传递到细胞核。我们在这里研究了具有功能的 MyD88 造血干细胞在阿尔茨海默病（AD）小鼠模型认知能力下降中的作用。我们使用辐照和移植野生型 GFP 细胞和 MyD88 缺陷型细胞生成了经典嵌合小鼠模型。移植 GFP 细胞基本上可以挽救认知障碍，而 MyD88 缺陷型细胞则显著加速了 APP(swe)/PS1 小鼠的记忆缺陷。此外，我们发现缺乏 MyD88 的单核细胞和小胶质细胞对 Aβ的吞噬反应存在功能障碍。
