Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases

Abstract

Protein misfolding and aggregation have been associated with several human diseases such as Alzheimer’s, Parkinson’s and familial amyloid polyneuropathy etc. In this study, anti-fibrillation activity of vitamin k3 and its effect on the kinetics of amyloid formation of hen egg white lysozyme (HEWL) and Aβ-42 peptide were investigated. Here, in combination with Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), transmission electron microscopy and cell cytotoxicity assay, we demonstrated that vitamin k3 significantly inhibits fibril formation as well as the inhibitory effect is dose dependent manner. Our experimental studies inferred that vitamin k3 exert its neuro protective effect against amyloid induced cytotoxicity through concerted pathway, modifying the aggregation formation towards formation of nontoxic aggregates. Molecular docking demonstrated that vitamin k3 mediated inhibition of HEWL and Aβ-42 fibrillogenesis may be initiated by interacting with proteolytic resistant and aggregation prone regions respectively. This work would provide an insight into the mechanism of protein aggregation inhibition by vitamin k3; pave the way for discovery of other small molecules that may exert similar effect against amyloid formation and its associated neurodegenerative diseases.

Amino group of salicylic acid exhibits enhanced inhibitory potential against insulin amyloid fibrillation with protective aptitude toward amyloid induced cytotoxicity

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Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic approach

“…CD spectra of proteins are receptive to secondary structure of proteins, and owing to this responsiveness to changes in secondary structure, CD spectroscopy is a tool employed to have an insight of the changes in protein structure after a ligand binds to it . CD spectra of alpha helix rich proteins show a peak at around 208 and 222 nm, while CD spectra show a peak at around 218 nm for proteins having beta sheets . The protein's conformation gets altered once ligand binds to the protein.…”

“…[25][26][27] CD spectra of alpha helix rich proteins show a peak at around 208 and 222 nm, while CD spectra show a peak at around 218 nm for proteins having beta sheets. 28 The protein's conformation gets altered once ligand binds to the protein. This altered protein conformation corresponds to altered CD spectra, and hence changes in CD spectra are quite evident after binding of a ligand to the protein.…”

Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti‐renal cancer drug

“…Base lining and analysis were done using Jasco J‐720 software . Far‐UV CD spectra were recorded in the wavelength range of 200 to 250 nm using quartz cuvette of 0.1 cm …”

“…13 Far-UV CD spectra were recorded in the wavelength range of 200 to 250 nm using quartz 14 cuvette of 0.1 cm. 15 3 | RESULTS AND DISCUSSION…”