title: Naturally occurring polyphenolic inhibitors of amyloid beta aggregation.
abstract: Alzheimer's disease is the most common neurodegenerative disease and is one of the main causes of death in developed countries. Consumption of foods rich in polyphenolics is strongly correlated with reduced incidence of Alzheimer's disease. Our study has investigated the biological activity of previously untested polyphenolic compounds in preventing amyloid β aggregation. The anti-aggregatory potential of these compounds was assessed using the Thioflavin-T assay, transmission electron microscopy, dynamic light scattering and size exclusion chromatography. Two structurally related compounds, luteolin and transilitin were identified as potent inhibitors of Aβ fibril formation. Computational docking studies with an X-ray derived oligomeric structure offer a rationale for the inhibitory activity observed and may facilitate development of improved inhibitors of Aβ aggregation and toxicity.
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: quentin.churches@csiro.au.
authors.forename: Quentin I
authors.initials: QI
authors.lastname: Churches
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Caine
authors.affiliation: CSIRO Materials Science and Engineering, Bag 10, Clayton South, Victoria 3169, Australia.
authors.forename: Kate
authors.initials: K
authors.lastname: Cavanagh
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Vidana Chandana
authors.initials: VC
authors.lastname: Epa
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Lynne
authors.initials: L
authors.lastname: Waddington
authors.affiliation: CSIRO Materials Science and Engineering, Bag 10, Clayton South, Victoria 3169, Australia.
authors.forename: C Elisabet
authors.initials: CE
authors.lastname: Tranberg
authors.affiliation: CSIRO Materials Science and Engineering, Bag 10, Clayton South, Victoria 3169, Australia.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Meyer
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Jose N
authors.initials: JN
authors.lastname: Varghese
authors.affiliation: CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Victor
authors.initials: V
authors.lastname: Streltsov
authors.affiliation: CSIRO Materials Science and Engineering, Bag 10, Clayton South, Victoria 3169, Australia; School of Chemical and Physical Sciences, Flinders University, Adelaide, SA 5042, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Duggan
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010446:Peptide Fragments / Q000378:metabolism*; D059808:Polyphenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D066329:Protein Aggregates / Q000187:drug effects*; D066263:Protein Aggregation, Pathological / Q000517:prevention & control; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D059808:Polyphenols; D066329:Protein Aggregates; C075222:amyloid beta-protein (1-42)
keywords: Amyloid; Amyloid-beta peptide; Flavonoid; Flavonol; Isoflavone; Polyphenol