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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PeerJ Inc.
2015-09-01
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| Online Access: | https://peerj.com/articles/1271.pdf |
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| author | Tomas Šneideris Lina Baranauskienė Jonathan G. Cannon Rasa Rutkienė Rolandas Meškys Vytautas Smirnovas |
| author_facet | Tomas Šneideris Lina Baranauskienė Jonathan G. Cannon Rasa Rutkienė Rolandas Meškys Vytautas Smirnovas |
| author_sort | Tomas Šneideris |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T07:03:27Z |
| format | Article |
| id | doaj.art-b1012f5598f04939a6007b9a1c2a2e59 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T07:03:27Z |
| publishDate | 2015-09-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
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| spelling | doaj.art-b1012f5598f04939a6007b9a1c2a2e592023-12-03T09:46:44ZengPeerJ Inc.PeerJ2167-83592015-09-013e127110.7717/peerj.1271Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivativesTomas Šneideris0Lina Baranauskienė1Jonathan G. Cannon2Rasa Rutkienė3Rolandas Meškys4Vytautas Smirnovas5Department of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, LithuaniaDepartment of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, LithuaniaDepartment of Natural Sciences and Engineering, Middle Georgia State University, Cochran, GA, USADepartment of Molecular Microbiology and Biotechnology, Vilnius University Institute of Biochemistry, Vilnius, LithuaniaDepartment of Molecular Microbiology and Biotechnology, Vilnius University Institute of Biochemistry, Vilnius, LithuaniaDepartment of Biothermodynamics and Drug Design, Vilnius University Institute of Biotechnology, Vilnius, LithuaniaA 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.https://peerj.com/articles/1271.pdfAmyloidFibrilInhibitorProtein aggregationFlavoneAmyloid beta |
| spellingShingle | Tomas Šneideris Lina Baranauskienė Jonathan G. Cannon Rasa Rutkienė Rolandas Meškys Vytautas Smirnovas Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives PeerJ Amyloid Fibril Inhibitor Protein aggregation Flavone Amyloid beta |
| title | Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives |
| title_full | Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives |
| title_fullStr | Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives |
| title_full_unstemmed | Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives |
| title_short | Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives |
| title_sort | looking for a generic inhibitor of amyloid like fibril formation among flavone derivatives |
| topic | Amyloid Fibril Inhibitor Protein aggregation Flavone Amyloid beta |
| url | https://peerj.com/articles/1271.pdf |
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