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Ultra rapid in vivo screening for anti-Alzheimer anti-amyloid drugs

机译:超快速体内筛选抗阿兹海默症抗淀粉样蛋白药物

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摘要

More than 46 million people worldwide suffer from Alzheimer’s disease. A large number of potential treatments have been proposed; among these, the inhibition of the aggregation of amyloid β-peptide (Aβ), considered one of the main culprits in Alzheimer’s disease. Limitations in monitoring the aggregation of Aβ in cells and tissues restrict the screening of anti-amyloid drugs to in vitro studies in most cases. We have developed a simple but powerful method to track Aβ aggregation in vivo in real-time, using bacteria as in vivo amyloid reservoir. We use the specific amyloid dye Thioflavin-S (Th-S) to stain bacterial inclusion bodies (IBs), in this case mainly formed of Aβ in amyloid conformation. Th-S binding to amyloids leads to an increment of fluorescence that can be monitored. The quantification of the Th-S fluorescence along the time allows tracking Aβ aggregation and the effect of potential anti-aggregating agents.
机译:全世界有4600万人患有阿尔茨海默氏病。已经提出了大量潜在的治疗方法。其中,抑制淀粉样β肽(Aβ)的聚集被认为是阿尔茨海默氏病的罪魁祸首之一。在大多数情况下,监测细胞和组织中Aβ聚集的局限性限制了抗淀粉样蛋白药物的筛选。我们已经开发出一种简单而强大的方法,利用细菌作为体内淀粉样蛋白储库来实时跟踪体内Aβ聚集。我们使用特定的淀粉样蛋白染料硫黄素-S(Th-S)对细菌包涵体(IBs)染色,在这种情况下,细菌包涵体主要由淀粉样构象的Aβ形成。 Th-S与淀粉样蛋白的结合导致可以监测的荧光增加。随时间对Th-S荧光的定量分析可以跟踪Aβ聚集和潜在的抗聚集剂的作用。

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