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Bioorg Med Chem Lett ; 24(14): 3108-12, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-24878198

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 ß 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 Aß 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 Aß aggregation and toxicity.


Subject(s)
Amyloid beta-Peptides/metabolism , Peptide Fragments/metabolism , Polyphenols/pharmacology , Protein Aggregates/drug effects , Crystallography, X-Ray , Dose-Response Relationship, Drug , Humans , Models, Molecular , Molecular Structure , Polyphenols/chemistry , Polyphenols/isolation & purification , Protein Aggregation, Pathological/prevention & control , Structure-Activity Relationship
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