Jess老年痴呆研究结果发表在Nature主刊

       文章：NLRP3 inflammasome activation drives tau pathology

       期刊：Nature volume 575, pages,669–673(2019)

       主要作者单位：

       1.Department of Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital of Bonn, Bonn, Germany.

       2.German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

        研究摘要

        阿尔茨海默病是Z主要的老年痴呆疾病，其特点是斑块状淀粉样蛋白-β的积累，神经原纤维缠结中过度磷酸化的Tau的聚集，以及神经炎症，共同导致神经变性和认知功能下降。NLRP3炎症小体在激活小胶质细胞内聚集，导致caspase-1和下游白细胞介素-1β，切割，释放和活性成熟。NLRP3炎症小体已被证明是必不可少的。

       淀粉样蛋白-β在小鼠模型疾病的发展和进展尚不清楚。在此，作者发现NLRP3炎性小体功能的丧失，通过调节tau磷酸酶和激酶，降低tau磷酸化和和聚集。Tau激活NLRP3炎性小体，脑内注射含纤维淀粉样蛋白的脑匀浆，以NLRP3依赖的方式诱导tau病理。这些数据确定了小胶质细胞和NLRP3炎性小体激活在阿尔茨海默病发病机制中的重要作用，并支持阿尔茨海默病的淀粉样细胞学假说，表明神经原纤维缠结发展为淀粉样β诱导的小胶质细胞激活的下游途径。

炎性小体在神经退行性疾病中作用示意图

炎性小体活化及信号通路示意图

       Jess检测条件培养基中分泌性Caspase-1

       实验方法

       For caspase-1 detection or collection of conditioned medium for neuronal experiments, 2 million microglia or 600,000 microglia per well were plated in a 6-well plate.caspase-1secretion by using a Jess system (ProteinSimple). Here, samples were run undiluted on a 12–230-kDa separation module according to the manufacturer’s instructions and detection was achieved by using a caspase-1 antibody (Adipogen) at 1:50. Data were analysed with Compass software version 4.0.0 (ProteinSimple).

       结果

        结果说明原文：Jess-based analysis of conditioned medium of LPS + tau wild-type-treated wild-type microglia stained for caspase-1. LPS/ATP-treated wild-type microglia served as positive control

       结果说明原文：Jess-based analysis of conditioned medium of primary wildtype,Asc–/– and Nlrp3–/– microglia primed with LPS and treated with the indicated forms of tau P301S. LPS/ATP-treated wild-type microglia served as positive control. Samples were stained for caspase-1.

（来源：ProteinSimple）