Title
Vitamin k3 inhibits protein aggregation: Implication in the treatment of amyloid diseases
Author
Parvez Alam, Sumit Kumar Chaturvedi, Mohammad Khursheed Siddiqi, Ravi Kant Rajpoot, Mohd Rehan Ajmal, Masihuz Zaman, Rizwan Hasan Khan
Year
2016
Journal
Scientific Reports
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.
Full Article
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Aggregation, Ligand binding, Thermal stability, Biochemistry