Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme

Su Chun How, Yu Hong Cheng, Chun Hsien Lo, Jinn Tsyy Lai, Ta Hsien Lin, Zuzana Bednarikova, Andrea Antosova, Zuzana Gazova*, Josephine W. Wu, Steven S.S. Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The 129-residue lysozyme has been shown to form amyloid fibrils in vitro. While methylene blue (MB), a compound in the phenothiazinium family, has been shown to dissemble tau fibril formation, its anti-fibrillogenic effect has not been thoroughly characterized in other proteins/peptides. This study examines the effects of MB on the in vitro fibrillogenesis of lysozyme at pH 2.0 and 55 °C. Our results demonstrated that, upon 7-day incubation, the plateau ThT fluorescence of the sample was found to be ~8.69% or ~2.98% of the control when the molar ratio of lysozyme to MB was at 1:1.11 or 1:3.33, respectively, indicating that the inhibitory potency of MB against lysozyme fibrillogenesis is positively correlated with its concentration. We also found that MB is able to destabilize the preformed lysozyme fibrils. Moreover, molecular docking and molecular dynamics simulations results revealed that MB's mechanism of fibril formation inhibition may be triggered by binding with lysozyme's aggregation-prone region. Results reported here provide solid support for MB's effect on amyloid fibrillogenesis. We believe the additional insights gained herein may pave way to the discovery of other small molecules that may have similar action toward amyloid fibril formation and its associated diseases.

Original languageEnglish
Pages (from-to)1059-1067
Number of pages9
JournalInternational Journal of Biological Macromolecules
Volume119
DOIs
StatePublished - Nov 2018

Keywords

  • Amyloid fibril
  • Inhibition
  • Methylene blue

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