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Anti-amyloidogenic properties of some phenolic compounds.

Porzoor A, Alford B, Hügel HM, Grando D, Caine J, Macreadie I - Biomolecules (2015)

Bottom Line: After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001).There was a significant reduction in the green fluorescence intensity associated with 14 compounds.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.

View Article: PubMed Central - PubMed

Affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. afsaneh.porzoor@rmit.edu.au.

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.

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Related in: MedlinePlus

TEM micrograph of Aβ42 co-incubated with selected compounds. (a) Morphological effects of selected compounds on chemically synthesized Aβ42 aggregation was investigated and compared with the control sample. (b) Micrograph of chemically synthesized Aβ42 in presence of salvianolic acid B; (c) rosmarinic acid; (d) 2,5-DHBA (gentisic acid); (e) 3,4-DHCA (caffeic acid); and (f) 3,4,5-THBA (gallic acid). Arrows show micelle (globular) structures, protofibrils, and fibrillar species of Aβ42. A micrograph showing other conformational species of peptide formed by the compound is highlighted in the yellow box. The structure of each compound is also shown on the micrograph. (Scale bars = 200 nm).
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biomolecules-05-00505-f005: TEM micrograph of Aβ42 co-incubated with selected compounds. (a) Morphological effects of selected compounds on chemically synthesized Aβ42 aggregation was investigated and compared with the control sample. (b) Micrograph of chemically synthesized Aβ42 in presence of salvianolic acid B; (c) rosmarinic acid; (d) 2,5-DHBA (gentisic acid); (e) 3,4-DHCA (caffeic acid); and (f) 3,4,5-THBA (gallic acid). Arrows show micelle (globular) structures, protofibrils, and fibrillar species of Aβ42. A micrograph showing other conformational species of peptide formed by the compound is highlighted in the yellow box. The structure of each compound is also shown on the micrograph. (Scale bars = 200 nm).

Mentions: The control Aβ42 sample resulted in highly ordered fibrillar structures (Figure 5a). Although none of the compounds completely prevented aggregation, the extent of protofibril and fibril formation varied in the presence of different compounds. Structures like sheets, globular, and short or long fibrils were formed as a result of the affect of the compounds on the Aβ42 conformation.


Anti-amyloidogenic properties of some phenolic compounds.

Porzoor A, Alford B, Hügel HM, Grando D, Caine J, Macreadie I - Biomolecules (2015)

TEM micrograph of Aβ42 co-incubated with selected compounds. (a) Morphological effects of selected compounds on chemically synthesized Aβ42 aggregation was investigated and compared with the control sample. (b) Micrograph of chemically synthesized Aβ42 in presence of salvianolic acid B; (c) rosmarinic acid; (d) 2,5-DHBA (gentisic acid); (e) 3,4-DHCA (caffeic acid); and (f) 3,4,5-THBA (gallic acid). Arrows show micelle (globular) structures, protofibrils, and fibrillar species of Aβ42. A micrograph showing other conformational species of peptide formed by the compound is highlighted in the yellow box. The structure of each compound is also shown on the micrograph. (Scale bars = 200 nm).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496683&req=5

biomolecules-05-00505-f005: TEM micrograph of Aβ42 co-incubated with selected compounds. (a) Morphological effects of selected compounds on chemically synthesized Aβ42 aggregation was investigated and compared with the control sample. (b) Micrograph of chemically synthesized Aβ42 in presence of salvianolic acid B; (c) rosmarinic acid; (d) 2,5-DHBA (gentisic acid); (e) 3,4-DHCA (caffeic acid); and (f) 3,4,5-THBA (gallic acid). Arrows show micelle (globular) structures, protofibrils, and fibrillar species of Aβ42. A micrograph showing other conformational species of peptide formed by the compound is highlighted in the yellow box. The structure of each compound is also shown on the micrograph. (Scale bars = 200 nm).
Mentions: The control Aβ42 sample resulted in highly ordered fibrillar structures (Figure 5a). Although none of the compounds completely prevented aggregation, the extent of protofibril and fibril formation varied in the presence of different compounds. Structures like sheets, globular, and short or long fibrils were formed as a result of the affect of the compounds on the Aβ42 conformation.

Bottom Line: After 24 h incubation with Aβ42, five compounds reduced thioflavin T (ThT) fluorescence, indicative of their anti-amyloidogenic propensity (p < 0.001).There was a significant reduction in the green fluorescence intensity associated with 14 compounds.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.

View Article: PubMed Central - PubMed

Affiliation: School of Applied Sciences, RMIT University, Bundoora, Victoria 3083, Australia. afsaneh.porzoor@rmit.edu.au.

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.

Show MeSH
Related in: MedlinePlus