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

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 v...

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Published in:PeerJ (San Francisco, CA) CA), 2015-09, Vol.3, p.e1271-e1271, Article e1271
Main Authors: Šneideris, Tomas, Baranauskienė, Lina, Cannon, Jonathan G, Rutkienė, Rasa, Meškys, Rolandas, Smirnovas, Vytautas
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid
Amyloid beta
Biochemistry
Biology
Biophysics
Catechin
Clinical trials
Diabetes therapy
Disease
Epigallocatechin-3-gallate
Fibril
Fibrils
Flavone
Flavones
Fluorescence
Inhibitor
Insulin
Neurochemistry
Neurosciences
Polypeptides
Polyphenols
Protein aggregation
Protein expression
Protein structure
Proteins
Secondary structure
Synuclein
Tea
β-Amyloid
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Summary: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.
ISSN:2167-8359
2167-8359
DOI:10.7717/peerj.1271