Anti-Amyloidogenic Properties of Some Phenolic Compounds

Biomolecules

Afsaneh Porzoor³  Benjamin Alford²  Helmut M. Hügel²  Danilla Grando³  Joanne Caine¹  Ian Macreadie³ 

[1] Materials Science and Engineering, CSIRO Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052, Australia; E-Mail:;School of Applied Sciences, RMIT University, Melbourne, Victoria 3000, Australia; E-Mails:;School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia; E-Mails:

关键词: Alzheimer’s disease;    Saccharomyces cerevisiae;    polyphenols;    AHP1;    anti-amyloidogenic;    danshen;   

DOI  :  10.3390/biom5020505

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.