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.
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Methylene blue was tried in Phase II clinical trials for mild-to-moderate AD for suppressing tau aggregation and has drawn criticism due to binding efficiency problems showing blue discolorations in urine.
“Due to problems with binding efficiency, which show up as blue discolorations in urine, methylene blue (labeled as 12, Figure 5), which was also tried in Phase II clinical trials for mild-to-moderate AD (for suppressing tau aggregation), has drawn a lot of criticism [168,169,170].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [170]
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- Authors
- How, S.-C., Cheng, Y.-H., Lo, C.-H., Lai, J.-T., Lin, T.-H., Bednarikova, Z., Antosova, A., Gazova, Z., Wu, J. W., & Wang, S. S.-S.
- Affiliations
- National Taiwan University (TW)
- Food Industry Research and Development Institute (TW)
- Taipei Veterans General Hospital (TW)
- Yuanpei University (TW)
- Corresponding author
- Wu, Josephine W.
- Wang, Steven S.-S.
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 119
- Pages
- 1059-1067
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W2885743982
- Cited by
- 25
- References
- 57
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 1
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Science and Technology (VEGA 2/0145/17, COST 083/14 actionBM1405, 2/0030/18, SAS-MOST JRP 2015/5)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- methylene blue, lysozyme, amyloid fibril formation, fibril destabilization, aggregation-prone regions, ThT fluorescence, molecular docking, molecular dynamics simulation
- MeSH terms
- Amyloid, Amyloidosis, Methylene Blue, Molecular Conformation, Muramidase, Protein Binding, Spectrum Analysis, Structure-Activity Relationship, Molecular Dynamics Simulation, Molecular Docking Simulation, Protein Aggregation, Pathological, Protein Aggregates
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