Biomolecules & Therapeutics, 2020, 28(2), , pp.145-151
2020
Details
- Autor(en) / Beteiligte
- Titel
- Polyphenolic Biflavonoids Inhibit Amyloid-Beta Fibrillation and Disaggregate Preformed Amyloid-Beta Fibrils
- Ist Teil von
- Biomolecules & Therapeutics, 2020, 28(2), , pp.145-151
- Ort / Verlag
- Korea (South): The Korean Society of Applied Pharmacology
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- Alzheimer's disease (AD) is a devastating neurodegenerative disease and a major cause of dementia in elderly individuals worldwide. Increased deposition of insoluble amyloid β (Aβ) fibrils in the brain is thought be a key neuropathological hallmark of AD. Many recent studies show that natural products such as polyphenolic flavonoids inhibit the formation of insoluble Aβ fibrils and/or destabilize β-sheet-rich Aβ fibrils to form non-cytotoxic aggregates. In the present study, we explored the structure-activity relationship of naturally-occurring biflavonoids on Aβ amyloidogenesis utilizing an thioflavin T assay with Aβ1-42 peptide which is prone to aggregate more rapidly to fibrils than Aβ1-40 peptide. Among the biflavonoids we tested, we found amentoflavone revealed the most potent effects on inhibiting Aβ1-42 fibrillization (IC : 0.26 µM), as well as on disassembling preformed Aβ1-42 fibrils (EC : 0.59 µM). Our structure-activity relationship study suggests that the hydroxyl groups of biflavonoid compounds play an essential role in their molecular interaction with the dynamic process of Aβ1-42 fibrillization. Our atomic force microscopic imaging analysis demonstrates that amentoflavone directly disrupts the fibrillar structure of preformed Aβ1-42 fibrils, resulting in conversion of those fibrils to amorphous Aβ1-42 aggregates. These results indicate that amentoflavone affords the most potent anti-amyloidogenic effects on both inhibition of Aβ1-42 fibrillization and disaggregation of preformed mature Aβ1-42 fibrils.