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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

Amyloid formation assayed by thioflavin T fluorescence. (a) Fibril formation of Aβ42 and the associated increase in in situ ThT fluorescence in presence and absence of compounds were measured at 0 h (baseline) (b) after 16 h (c) and after 24 h incubation; (d) Selected phenolic compounds that resulted in a significant anti-amyloidogenic property compared with the positive control (EGCG) and negative control (Aβ42 & vehicle buffer) determined by ThT measured at 0, 16, and 24 h after incubation with chemically synthesized Aβ42. Significant differences are indicated: * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.001.
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biomolecules-05-00505-f001: Amyloid formation assayed by thioflavin T fluorescence. (a) Fibril formation of Aβ42 and the associated increase in in situ ThT fluorescence in presence and absence of compounds were measured at 0 h (baseline) (b) after 16 h (c) and after 24 h incubation; (d) Selected phenolic compounds that resulted in a significant anti-amyloidogenic property compared with the positive control (EGCG) and negative control (Aβ42 & vehicle buffer) determined by ThT measured at 0, 16, and 24 h after incubation with chemically synthesized Aβ42. Significant differences are indicated: * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.001.

Mentions: At the baseline (0 h) the starting fluorescent intensity was significantly lower in a positive control (EGCG) compared with Aβ42 and vehicle buffer (p < 0.01; Figure 1a). A similar effect was also viewed in the presence of caffeic acid trimers (BA_PG65, BA_PG69), chalcone (BA_PG84), and—to lesser extent—the Benzo[b]furan derivative (BA_PG83) (p < 0.05). Benzofuran-based compounds have previously been shown to exhibit potential aggregation and neurotoxicity inhibition effect against Aβ42 [39,40].


Anti-amyloidogenic properties of some phenolic compounds.

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

Amyloid formation assayed by thioflavin T fluorescence. (a) Fibril formation of Aβ42 and the associated increase in in situ ThT fluorescence in presence and absence of compounds were measured at 0 h (baseline) (b) after 16 h (c) and after 24 h incubation; (d) Selected phenolic compounds that resulted in a significant anti-amyloidogenic property compared with the positive control (EGCG) and negative control (Aβ42 & vehicle buffer) determined by ThT measured at 0, 16, and 24 h after incubation with chemically synthesized Aβ42. Significant differences are indicated: * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

biomolecules-05-00505-f001: Amyloid formation assayed by thioflavin T fluorescence. (a) Fibril formation of Aβ42 and the associated increase in in situ ThT fluorescence in presence and absence of compounds were measured at 0 h (baseline) (b) after 16 h (c) and after 24 h incubation; (d) Selected phenolic compounds that resulted in a significant anti-amyloidogenic property compared with the positive control (EGCG) and negative control (Aβ42 & vehicle buffer) determined by ThT measured at 0, 16, and 24 h after incubation with chemically synthesized Aβ42. Significant differences are indicated: * p < 0.05; ** p < 0.01; *** p < 0.005; **** p < 0.001.
Mentions: At the baseline (0 h) the starting fluorescent intensity was significantly lower in a positive control (EGCG) compared with Aβ42 and vehicle buffer (p < 0.01; Figure 1a). A similar effect was also viewed in the presence of caffeic acid trimers (BA_PG65, BA_PG69), chalcone (BA_PG84), and—to lesser extent—the Benzo[b]furan derivative (BA_PG83) (p < 0.05). Benzofuran-based compounds have previously been shown to exhibit potential aggregation and neurotoxicity inhibition effect against Aβ42 [39,40].

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