Kinetic and thermodynamic insights into the interaction of Aβ1–42 with astaxanthin and aggregation behavior of Aβ1–42: Surface plasmon resonance, microscopic, and molecular docking studies

Publication year: 2021
Authors: Moharram Dehghani a, Razieh Jalal a,b, Mohammad-Reza Rashidi c

a - Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
b - Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
c - Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

Published in: Biophysical Chemistry, 2021, Vol.275, p. 106612
doi: 10.1016/j.bpc.2021.106612

Amyloid-β 1–42 (Aβ1–42) aggregation is considered as an important process in the pathology of Alzheimer's disease (AD). Astaxanthin (ATX), a xanthophyll carotenoid, has a broad range of biological activities such as neuroprotective one. The present study aimed to elucidate the interaction of ATX with Aβ1–42, as well as its effect on Aβ1–42 aggregates under different conditions. Based on the surface plasmon resonance (SPR) results, ATX possessed a high affinity towards Aβ1–42 and the binding process was spontaneous, endothermic, and entropy-driven. Additionally, the binding affinity of ATX to Aβ1–42 was glucose and insulin concentration-dependent. Hydrophobic interactions may play an important role in the interaction between ATX and Aβ1–42. The results of SPR, thioflavin T (ThT), and transmission electron microscopy (TEM) analyses represented the dependency of the anti-amyloid activity of ATX on glucose, insulin, and ATX concentrations. Further, molecular docking results indicated the presence of some same binding sites on Aβ1–42 for ATX and glucose, as well as ATX and insulin, which suggests the possible competition between the molecules for Aβ1–42 binding. Furthermore, the MTT results confirmed that ATX effect on the viability of Aβ1–42-treated PC12 cells was dependent on glucose, insulin, and ATX concentrations. In general, the results provided further insights into the interaction between Aβ1–42 and ATX, as well as the effect of ATX on Aβ1–42 aggregates under various conditions.

MP-SPR keywords: Au sensor slide, binding, fixed angle, peptide - small molecule interaction