title: Different fates of Alzheimer's disease amyloid-β fibrils remodeled by biocompatible small molecules.
abstract: Amyloid fibrils implicated in numerous human diseases are thermodynamically very stable. Stringent conditions that would not be possible in a physiological environment are often required to disrupt the stable fibrils. Recently, there is increasing evidence that small molecules can remodel amyloid fibrils in a physiologically relevant manner. In order to investigate possible fibril remodeling mechanisms using this approach, we performed comparative studies on the structural features of the different amyloid-β (Aβ) aggregates remodeled from Aβ fibrils by three biocompatible small molecules: methylene blue; brilliant blue G; and erythrosine B. Combined with circular dichroism (CD), immuno-blotting, transmission electron microscopy (TEM), and atomic force microscopy (AFM) results, it was found that brilliant blue G- and erythrosine B-treatment generate fragmented Aβ fibrils and protofibrils, respectively. In contrast, incubation of the Aβ fibrils with methylene blue perturbs fibrillar structure, leading to amorphous Aβ aggregates. Our findings provide insights on the molecular mechanism of amyloid fibril formation and remodeling and also illustrate the possibility of controlled changes in biomolecule nanostructures.
authors.affiliation: Department of Chemical Engineering, University of Virginia, Charlottesville, VA 22904-4741, USA.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Irwin
authors.forename: H Edward
authors.initials: HE
authors.lastname: Wong
authors.forename: Inchan
authors.initials: I
authors.lastname: Kwon
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D001672:Biocompatible Materials / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D001672:Biocompatible Materials