A chemical screening approach reveals that indole fluorescence is quenched by pre-fibrillar but not fibrillar amyloid-beta.
Aggregated amyloid-beta (Abeta) peptide is implicated in the pathology of Alzheimer's disease. In vitro and in vivo, these aggregates are found in a variety of morphologies, including globular oligomers and linear fibrils, which possess distinct biological activities. However, known chemical probes, including the dyes thioflavin T and Congo Red, appear to lack selectivity for specific amyloid structures. To identify molecules that might differentiate between these architectures, we employed a fluorescence-based interaction assay to screen a collection of 68 known Abeta ligands against pre-formed oligomers and fibrils. In these studies, we found that the fluorescence of five indole-based compounds was selectively quenched ( approximately 15%) in the presence of oligomers, but remained unchanged after addition of fibrils. These results suggest that indoles might be complementary to existing chemical probes for studying amyloid formation in vitro.
Reinke
Ashley A
AA
Departments of Biological Chemistry, Pathology and The Life Sciences Institute, University of Michigan, 210 Washtenaw Ave., Ann Arbor, MI 48109-2216, USA.
Seh
Han Yiau
HY
Gestwicki
Jason E
JE
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D004396:Coloring Agents / Q000737:chemistry; D003224:Congo Red / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013844:Thiazoles / Q000737:chemistry
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D007211:Indoles; D013844:Thiazoles; C009462:thioflavin T; D003224:Congo Red