Department of Neurobiology, Sagol School of Neuroscience, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 699788, Israel.
Nat Commun. 2013;4:2030. doi: 10.1038/ncomms3030.
In Alzheimer's disease, soluble amyloid-β causes synaptic dysfunction and neuronal loss. Receptors involved in clearance of soluble amyloid-β are not known. Here we use short hairpin RNA screening and identify the scavenger receptor Scara1 as a receptor for soluble amyloid-β expressed on myeloid cells. To determine the role of Scara1 in clearance of soluble amyloid-β in vivo, we cross Scara1 null mice with PS1-APP mice, a mouse model of Alzheimer's disease, and generate PS1-APP-Scara1-deficient mice. Scara1 deficiency markedly accelerates Aβ accumulation, leading to increased mortality. In contrast, pharmacological upregulation of Scara1 expression on mononuclear phagocytes increases Aβ clearance. This approach is a potential treatment strategy for Alzheimer's disease.
在阿尔茨海默病中，可溶性淀粉样蛋白-β导致突触功能障碍和神经元丧失。目前尚不清楚参与清除可溶性淀粉样蛋白-β的受体。在这里，我们使用短发夹 RNA 筛选并鉴定出清道夫受体 Scara1 是表达在髓样细胞上的可溶性淀粉样蛋白-β的受体。为了确定 Scara1 在体内清除可溶性淀粉样蛋白-β中的作用，我们将 Scara1 缺失小鼠与 PS1-APP 小鼠（阿尔茨海默病的小鼠模型）杂交，并生成 PS1-APP-Scara1 缺失小鼠。Scara1 缺失显著加速了 Aβ 的积累，导致死亡率增加。相比之下，单核吞噬细胞上 Scara1 表达的药物上调增加了 Aβ 的清除。这种方法是治疗阿尔茨海默病的一种潜在策略。
