Cholinium-Based Ionic Liquids Attenuate the Amyloid Fibril Formation of Lysozyme: A Greener Concept of Antiamyloidogenic Ionic Liquids

Amyloid fibrils share dominant ,g-sheet structures that form pathological deposits in human organs causing various debilitating neurodegenerative diseases such as type II diabetes, Huntington's, Alzheimer's, and Parkinson's diseases, and thus, the treatment of these amyloid-based diseases is a major overriding concern. Ionic liquids (ILs), being biocompatible solvent medium for proteins, have been introduced as effective antiamyloidogenic agents to prevent the fibrillation process; bio-derived cholinium-based ILs ([Chn] ILs) deserve special attention in view of their inhibitory action on protein amyloid formation to enable the restoration of its biochemical function. Herein, the antiamyloido-genic action of four [Chn] ILs, namely cholinium acetate [Chn][Ac], cholinium bitartarate [Chn][Bit], cholinium chloride [Chn][Cl], and cholinium dihydrogen phosphate [Chn][Dhp], on the in vitro amyloid formation of the lysozyme (Lys) was investigated by applying ThT fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy. Additionally, transmission electronic microscopy (TEM), dynamic light scattering (DLS), and atomic force microscopy (AFM) measurements were also performed to ascertain the morphological changes. Interestingly, with incubation of Lys without ILs there was a substantial increase in thioflavin T (ThT) fluorescence intensity for the Lys, confirming the formation of Lys fibrillar aggregates. The results of FT-IR and UV-CD measurements showed that the Lys secondary structure was retained in the presence of the [Chn][Bit] and [Chn][DHP] ILs, which was lost in the absence of these ILs in the incubating conditions. It was further inferred by morphological analysis via TEM, AFM, and DLS that through thermochemical treatment of Lys, fibrils were formed, and these [Chn] ILs exhibit an increased propensity to suppress the formation of mature fibrils. Overall, the inhibition efficiency of these [Chn] ILs is accredited to the bio-derived cholinium cations as well as the nature of anions based on Hofmeister series. The present study offers a deep insight into the role of ILs in controlling the fibril formation in proteins and thus, they may serve as agents to remediate neurodegenerative diseases.

Automated summary

The study found that bio-derived cholinium-based ionic liquids have inhibitory effects on the amyloid formation of lysozyme, preventing fibrillation and potentially serving as a new treatment for neurodegenerative diseases.