Molecular Basis of the Inhibition and Disaggregation of Thermally-induced Amyloid Fibrils of Human Serum Albumin by an Anti-Parkinson's Drug, Benserazide Hydrochloride
Inhibition, Disaggregation, Amyloid fibrils, Interaction, Combined quenching
Digital Object Identifier (DOI)
This study summarises the results of multifactorial analysis of the inhibition/destabilization of human serum albumin (HSA) amyloid fibrils by an anti-Parkinson's drug, benserazide hydrochloride (BH). Different biophysical techniques have been utilized for this purpose. Rayleigh light scattering (RLS) and dynamic light scattering (DLS) confirmed the formation of aggregates, that were identified as amyloid fibrils by the thioflavin T (ThT) and Congo Red (CR) fluorescent dye binding assays. Formation of amyloid fibrils and their inhibition/disaggregation was further characterized by transmission electron microscopy (TEM). The cytoprotective role of BH was examined by cytotoxicity assay performed on the SH-SY5Y neuronal cells. The deviation from linearity in the Stern Volmer plot indicated the presence of static and dynamic quenching of the HSA intrinsic fluorescence by BH. The value of Kd obtained by Scatchard plot was 4.5 × 10−4 M. The changes in the Trp microenvironment caused by the BH binding were further characterized by the synchronous fluorescence spectroscopy. Circular dichroism (CD) and differential scanning calorimetry (DSC) indicated increased HSA stability when bound to BH. Multiple binding sites in human serum albumin (HSA) for BH were found by binding and docking analysis, which revealed the involvement of hydrophobic and hydrogen bonding in the HSA-BH complex formation. Further, the negativity of the binding free energy suggested the spontaneity of the BH-HSA interaction. Overall, our study indicated that BH can serve as an efficient inhibitor/destabilizer of amyloid fibrils and the possible mechanism of this efficiency includes stabilization of HSA in the presence of BH. Therefore, BH can be used in treatment of systemic amyloidoses, since this drug cannot cross blood brain barrier (BBB).
Was this content written or created while at USF?
Citation / Publisher Attribution
Journal of Molecular Liquids, v. 278, p. 553-567
Scholar Commons Citation
Chandel, Tajalli Ilm; Masroor, Aiman; Siddiqi, Mohammad Khursheed; Siddique, Ibrar Ahmad; Jahan, Ishrat; Ali, Maroof; Nayeem, Shahid M.; Uversky, Vladimir N.; and Khan, Rizwan Hasan, "Molecular Basis of the Inhibition and Disaggregation of Thermally-induced Amyloid Fibrils of Human Serum Albumin by an Anti-Parkinson's Drug, Benserazide Hydrochloride" (2019). Molecular Medicine Faculty Publications. 140.