Inhibitory as well as Disaggregation Potential of Selected Hydroxy Benzoic Phytochemicals on Hen Egg-White Lysozyme Amyloidogenesis

Background: Amyloids are a class of ordered protein aggregates which have been implicated in the onset of several degenerative diseases, such as Alzheimer's disease, Parkinson's disease, Type II diabetes, and so on. Despite extensive research, the exact mechanism and the driving factors for the amyloidogenesis process remain elusive. Identifying molecules which can effectively inhibit and/or disaggregate the fibrils may be one effective therapeutic strategy against amyloidosis. Objectives: In the current study, few hydroxy-benzoic phytochemicals were selected to study their effects on the formation as well as disaggregation of Hen Egg-White Lysozyme (HEWL) amyloids, namely gallic acid, syringic acid, vanillic acid, and iso-vanillic acid. Methods: Amyloidogenesis was monitored using methods like the thioflavin T assay, Field Emission Scanning Electron Microscopy (FESEM), and dynamic light scattering (DLS) studies. Further protein conformational changes were monitored using methods like 8-Anilino-Naphthalene-1-Sulfonate (ANS) fluorescence, Circular Dichroism (CD) spectroscopy, and guanidine hydrochloride mediated stability studies. Computational approach was also employed to get an insight on the interaction(s) between the selected compounds and HEWL using docking studies. Results: The selected compounds exhibited significant inhibitory as well as disaggregation effects on HEWL amyloids. Interaction with the phytochemicals was also associated with considerable conformational changes in HEWL. Docking studies show the role of hydrogen bonding between HEWL and the phytochemicals. Conclusion: Thus, the current study throws light on the key factors that drive amyloid formation and hence will be helpful in the development of effective therapeutics against amyloidosis.

Automated summary

In this study, various hydroxy-benzoic phytochemicals were investigated for their effects on the formation and disaggregation of HEWL amyloids. The compounds showed significant inhibitory and disaggregation effects on the amyloids, with interactions involving hydrogen bonding. Computational docking studies provided insights into the molecular interactions between the selected compounds and HEWL, highlighting their potential as therapeutic agents against amyloidosis.