Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme.

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.

journal_name

Int J Biol Macromol

authors

How SC,Cheng YH,Lo CH,Lai JT,Lin TH,Bednarikova Z,Antosova A,Gazova Z,Wu JW,Wang SS

doi

10.1016/j.ijbiomac.2018.08.038

subject

Has Abstract

pub_date

2018-11-01 00:00:00

pages

1059-1067

eissn

0141-8130

issn

1879-0003

pii

S0141-8130(18)32680-1

journal_volume

119

pub_type

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