title: Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives.
abstract: A range of diseases is associated with amyloid fibril formation. Despite different proteins being responsible for each disease, all of them share similar features including beta-sheet-rich secondary structure and fibril-like protein aggregates. A number of proteins can form amyloid-like fibrils in vitro, resembling structural features of disease-related amyloids. Given these generic structural properties of amyloid and amyloid-like fibrils, generic inhibitors of fibril formation would be of interest for treatment of amyloid diseases. Recently, we identified five outstanding inhibitors of insulin amyloid-like fibril formation among the pool of 265 commercially available flavone derivatives. Here we report testing of these five compounds and of epi-gallocatechine-3-gallate (EGCG) on aggregation of alpha-synuclein and beta-amyloid. We used a Thioflavin T (ThT) fluorescence assay, relying on halftimes of aggregation as the measure of inhibition. This method avoids large numbers of false positive results. Our data indicate that four of the five flavones and EGCG inhibit alpha-synuclein aggregation in a concentration-dependent manner. However none of these derivatives were able to increase halftimes of aggregation of beta-amyloid.
authors.affiliation: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology , Vilnius , Lithuania.
authors.forename: Tomas
authors.initials: T
authors.lastname: Šneideris
authors.affiliation: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology , Vilnius , Lithuania.
authors.forename: Lina
authors.initials: L
authors.lastname: Baranauskienė
authors.affiliation: Department of Natural Sciences and Engineering, Middle Georgia State University , Cochran, GA , USA.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Cannon
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Vilnius University Institute of Biochemistry , Vilnius , Lithuania.
authors.forename: Rasa
authors.initials: R
authors.lastname: Rutkienė
authors.affiliation: Department of Molecular Microbiology and Biotechnology, Vilnius University Institute of Biochemistry , Vilnius , Lithuania.
authors.forename: Rolandas
authors.initials: R
authors.lastname: Meškys
authors.affiliation: Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology , Vilnius , Lithuania.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Smirnovas
keywords: Alpha-synuclein; Amyloid; Amyloid beta; Fibril; Flavone; Inhibitor; Protein aggregation