Angew. Chem. Int. Ed. http://doi.org/f2xrdh (2014)
The presence of amyloid fibrils is characteristic of several diseases, including Alzheimer disease and type 2 diabetes. Hence, the formation of the peptide dimers and oligomers, which subsequently aggregate to make these fibrils, is an important process to monitor and understand. Now, Ehud Gazit and colleagues report an assay with the ability to detect dimerization of three amyloidogenic polypeptide monomers; human islet amyloid polypeptide, β-amyloid or α-synuclein. The bimolecular fluorescence complementation assay relies on fluorescence signals only resulting from dimeric interaction between the amyloidogenic peptides, which are fused, via a linker, to fragments of a split mCherry protein. The assay identified compounds already known to inhibit aggregation of amyloid peptides and these compounds were then shown to increase the viability of pancreatic cells in the presence of amyloid fibrils in a dose-dependent manner. The correlation between the screening process and in vitro results indicates that these dimeric interactions are an important target for drug development. The assay has the potential to be automated, thus permitting high-throughput screening of compounds.
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