title: A chemical screening approach reveals that indole fluorescence is quenched by pre-fibrillar but not fibrillar amyloid-beta.
abstract: 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.
authors.affiliation: Departments of Biological Chemistry, Pathology and The Life Sciences Institute, University of Michigan, 210 Washtenaw Ave., Ann Arbor, MI 48109-2216, USA.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Reinke
authors.forename: Han Yiau
authors.initials: HY
authors.lastname: Seh
authors.forename: Jason E
authors.initials: JE
authors.lastname: Gestwicki
mesh_terms: 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
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D005456:Fluorescent Dyes; D007211:Indoles; D013844:Thiazoles; C009462:thioflavin T; D003224:Congo Red