title: 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.
authors.affiliation: Molecular Biophysics and Biophysical Chemistry Group, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Alam
authors.affiliation: Molecular Biophysics and Biophysical Chemistry Group, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Sumit Kumar
authors.initials: SK
authors.lastname: Chaturvedi
authors.affiliation: Molecular Biophysics and Biophysical Chemistry Group, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Mohammad Khursheed
authors.initials: MK
authors.lastname: Siddiqi
authors.affiliation: Recombinant Gene Product Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067, India.
authors.forename: Ravi Kant
authors.initials: RK
authors.lastname: Rajpoot
authors.affiliation: Molecular Biophysics and Biophysical Chemistry Group, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Mohd Rehan
authors.initials: MR
authors.lastname: Ajmal
authors.affiliation: Molecular Biophysics and Biophysical Chemistry Group, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Masihuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: Molecular Biophysics and Biophysical Chemistry Group, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh-202002, India.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D002645:Chickens; D006801:Humans; D009113:Muramidase / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000188:drug therapy / Q000378:metabolism*; D024483:Vitamin K 3 / Q000008:administration & dosage*
chemical_list: D016229:Amyloid beta-Peptides; D024483:Vitamin K 3; C421864:hen egg lysozyme; D009113:Muramidase