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

PeerJ

Vytautas Smirnovas¹  Tomas Šneideris¹  Lina Baranauskienė¹  Rolandas Meškys²  Rasa Rutkienė²  Jonathan G. Cannon³ 

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

关键词: Amyloid;    Fibril;    Inhibitor;    Protein aggregation;    Flavone;    Amyloid beta;   

DOI  :  10.7717/peerj.1271

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown