Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer's disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of and promoting disaggregation of fibrils. In the present study, we further sought to investigate the structural basis of the disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of fibril via the π-π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer's disease.


Peter K Windsor, Stephen P Plassmeyer, Dominic S Mattock, Jonathan C Bradfield, Erika Y Choi, Bill R Miller, Byung Hee Han. Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation. International journal of molecular sciences. 2021 Mar 12;22(6)

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 33809196

View Full Text