Anti-Amyloidogenic Properties of Some Phenolic Compounds
| Autor: | Ian Macreadie, Danilla Grando, Joanne M. Caine, Helmut M. Hügel, Benjamin L. Alford, Afsaneh Porzoor |
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| Rok vydání: | 2015 |
| Předmět: |
Amyloid
Stereochemistry Amyloid beta Proteolysis Saccharomyces cerevisiae lcsh:QR1-502 Salvia miltiorrhiza Peptide Biochemistry lcsh:Microbiology Article anti-amyloidogenic Green fluorescent protein Small Molecule Libraries chemistry.chemical_compound medicine Molecular Biology polyphenols chemistry.chemical_classification AHP1 Amyloid beta-Peptides medicine.diagnostic_test biology Plant Extracts Peroxiredoxins biology.organism_classification danshen Peptide Fragments Yeast chemistry biology.protein Thioflavin Alzheimer’s disease |
| Zdroj: | Biomolecules Volume 5 Issue 2 Pages 505-527 Biomolecules, Vol 5, Iss 2, Pp 505-527 (2015) |
| ISSN: | 2218-273X |
| DOI: | 10.3390/biom5020505 |
| Popis: | A family of 21 polyphenolic compounds consisting of those found naturally in danshen and their analogues were synthesized and subsequently screened for their anti-amyloidogenic activity against the amyloid beta peptide (Aβ42) of Alzheimer’s disease. After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001). TEM and immunoblotting analysis also showed that selected compounds were capable of hindering fibril formation even after prolonged incubations. These compounds were also capable of rescuing the yeast cells from toxic changes induced by the chemically synthesized Aβ42. In a second assay, a Saccharomyces cerevisiae AHP1 deletant strain transformed with GFP fused to Aβ42 was treated with these compounds and analyzed by flow cytometry. There was a significant reduction in the green fluorescence intensity associated with 14 compounds. We interpret this result to mean that the compounds had an anti-amyloid-aggregation propensity in the yeast and GFP-Aβ42 was removed by proteolysis. The position and not the number of hydroxyl groups on the aromatic ring was found to be the most important determinant for the anti-amyloidogenic properties. |
| Databáze: | OpenAIRE |
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