Mechanistic insight into inhibition of amyloid fibrillation of human serum albumin by Vildagliptin

Protein aggregation leads to several human pathologies such as Alzheimer’s disease (AD), type 2 diabetes (T2D), Parkinson’s disease (PD), etc. Due to the overlap in the mechanisms of type 2 diabetes and brain disorders, common effective pharmacological interventions to treat both T2D and AD is under...

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Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2022-08, Vol.216, p.112563-112563, Article 112563
Main Authors: Malik, Sadia, Zaidi, Nida, Siddiqi, Mohammad Khursheed, Majid, Nabeela, Masroor, Aiman, Salam, Samreen, Khan, Rizwan H.
Format: Article
Language:English
Subjects:
Amyloid
Dipeptidyl peptidase-4
Thioflavin T assay
Vildagliptin
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Summary:Protein aggregation leads to several human pathologies such as Alzheimer’s disease (AD), type 2 diabetes (T2D), Parkinson’s disease (PD), etc. Due to the overlap in the mechanisms of type 2 diabetes and brain disorders, common effective pharmacological interventions to treat both T2D and AD is under extensive research. Therefore, major aim of research is to repurpose already established treatment of diabetes to cure AD as well. This study evaluates mechanistic insight into anti-amyloidogenic potential of anti-diabetic drug Vildagliptin (VLD) on human serum albumin fibrillation (HSA) by using biophysical, calorimetric, imaging techniques along with hemolytic assay. Dynamic light scattering (DLS) and Rayleigh light scattering (RLS) results showed presence of few small-sized aggregates in the presence of VLD which are formed by deaccelerating the amyloidogenesis as shown by thioflavin T (ThT) fluorescence and Congo red (CR) binding assay. Further, Isothermal titration calorimetry (ITC), steady state fluorescence quenching, molecular docking results revealed that VLD form complex with amyloid facilitating state of HSA and consequently mask the hydrophobic residues involved in amyloidogenesis as evident from decrease in ANS fluorescence. Differential scanning calorimetry (DSC) results confirm that VLD stabilizes the amyloid facilitating state of HSA. In addition, SEM images demonstrated that VLD alleviates the hemolytic effect induced by fibrils of HSA. This study reports VLD as a potential inhibitor of amyloid fibrillation and provides promising results to repurpose VLD as a drug candidate for the cure of Alzheimer’s diseases along with diabetes. [Display omitted] •VLD binds and interferes with HSA amyloidogenesis.•Anti-amyloidogenic potenial of VLD established by biophysical methods.•VLD is a potent amyloid inhibitor of HSA.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2022.112563