title: Anti-amyloidogenic properties of some phenolic compounds.
abstract: 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.
authors.affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. afsaneh.porzoor@rmit.edu.au.
authors.forename: Afsaneh
authors.initials: A
authors.lastname: Porzoor
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne, Victoria 3000, Australia. ben.alford@amptechpl.com.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Alford
authors.affiliation: School of Applied Sciences, RMIT University, Melbourne, Victoria 3000, Australia. helmut.hugel@rmit.edu.au.
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Hügel
authors.affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. danilla.grando@rmit.edu.au.
authors.forename: Danilla
authors.initials: D
authors.lastname: Grando
authors.affiliation: Materials Science and Engineering, CSIRO Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052, Australia. Jo.Caine@csiro.au.
authors.forename: Joanne
authors.initials: J
authors.lastname: Caine
authors.affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. ian.macreadie@rmit.edu.au.
authors.forename: Ian
authors.initials: I
authors.lastname: Macreadie
mesh_terms: D000682:Amyloid / Q000187:drug effects*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D010446:Peptide Fragments / Q000633:toxicity; D054464:Peroxiredoxins / Q000235:genetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D059808:Polyphenols / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C515936:AHP1 protein, S cerevisiae; D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010936:Plant Extracts; D059808:Polyphenols; D054852:Small Molecule Libraries; C442220:amyloid beta-protein (2-42); D054464:Peroxiredoxins