Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives

Tomas Šneideris; Lina Baranauskienė; Jonathan G Cannon; Rasa Rutkienė; Rolandas Meškys; Vytautas Smirnovas

doi:10.7717/peerj.1271

Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives

PeerJ. 2015 Sep 24:3:e1271. doi: 10.7717/peerj.1271. eCollection 2015.

Authors

Tomas Šneideris¹, Lina Baranauskienė¹, Jonathan G Cannon², Rasa Rutkienė³, Rolandas Meškys³, Vytautas Smirnovas¹

Affiliations

¹ Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology , Vilnius , Lithuania.
² Department of Natural Sciences and Engineering, Middle Georgia State University , Cochran, GA , USA.
³ Department of Molecular Microbiology and Biotechnology, Vilnius University Institute of Biochemistry , Vilnius , Lithuania.

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.

Keywords: Alpha-synuclein; Amyloid; Amyloid beta; Fibril; Flavone; Inhibitor; Protein aggregation.

Grants and funding

This research was funded by the European Social Fund under the Global Grant Measure, project number VP1-3.1-ŠMM-07-K-02-020. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.