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

Abstract

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. Method: 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. Result: The selected compounds exhibited significant inhibitory as well as disaggregation effects on HEWL amyloids. In-teraction with the phytochemicals was also associated with considerable conformational changes in HEWL. Docking studies show 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 for development of effective therapeutics against amyloidosis.