Alpha-cyclodextrin turns SDS-induced amyloid fibril into native-like structure

Amyloid fibril formation causes multiple neurodegenerative diseases and its possible therapy is still not available. The aim of this study was to determine the solubilizing and refolding potential of alpha cyclodextrin (alpha-CD) on SDS-induced amyloid fibril formation of lysozyme at pH 7.4 using turbidity, intrinsic fluorescence, dynamic light scattering (DLS), ThT binding assay, far-UV circular dichroism, and molecular docking. Spectroscopic data showed that lysozyme forms amyloid-like aggregates in the presence of 03 mM SDS at pH 7.4. SDS-induced lysozyme fibrils were solubilized by alpha-CD in a dose-dependent manner. At concentrations lower than 1.0 mM, alpha-CD was unable to solubilize SDS-induced lysozyme fibrils, while higher concentrations of alpha-CD produced complete solubilization. Far-UV CD and intrinsic fluorescence data suggest that the secondary and tertiary structures of lysozyme were restored at higher alpha-CD concentrations. The hydrodynamic radius was found to increase in the presence of SDS and radius is restored in the presence alpha-CD. Molecular docking data suggest that alpha-CD binds the same site on lysozyme as that occupied by SDS, albeit with higher affinity. Moreover, molecular docking between SDS and alpha-CD shows a direct contact via hydrogen bonding between O-atom of SDS and -OH group of alpha-CD. We hypothesize that the higher affinity of alpha-CD towards the binding site on lysozyme along with its direct interaction with SDS allows it to act as a chemical chaperone displacing SDS. The mechanisms underlying this action of alpha-CD may provide a foundation for the identification of drugs for the suppression of fibrillogenesis. (C) 2019 Elsevier B.V. All rights reserved.