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Designed Amyloid β Peptide Fibril—A Tool for High-Throughput Screening of Fibril Inhibitors

✍ Scribed by Gunnar T. Dolphin; Myriam Ouberai; Pascal Dumy; Julian Garcia


Publisher
John Wiley and Sons
Year
2007
Tongue
English
Weight
502 KB
Volume
2
Category
Article
ISSN
1860-7179

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✦ Synopsis


Abstract

Amyloid β peptide (Aβ) fibril formation is widely believed to be the causative event of Alzheimer’s disease pathogenesis. Therapeutic approaches are therefore in development that target various sites in the production and aggregation of Aβ. Herein we present a high‐throughput screening tool to generate novel hit compounds that block Aβ fibril formation. This tool is an application for our fibril model (Aβ~16–37~Y~20~K~22~K~24~)~4~, which is a covalent assembly of four Aβ fragments. With this tool, screening studies are complete within one hour, as opposed to days with native Aβ~1–40~. A Z′ factor of 0.84±0.03 was determined for fibril formation and inhibition, followed by the reporter molecule thioflavin T. Herein we also describe the analysis of a broad range of reported inhibitors and non‐inhibitors of Aβ fibril formation to test the validity of the system.


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