Background: The abnormal folding and aggregation of the amyloid-β is a hallmark of neurodegenerative disorders such as Alzheimer’s disease (AD). The use of natural compounds with anti-aggregation properties is an attractive strategy to treat the neurodegenerative diseases. Astaxanthin (ATX), a xanthophyll carotenoid with powerful antioxidant activity, has been found to have the protective effect on amyloid β (Aβ) aggregation. The aim of this study was to obtain the kinetic and thermodynamic parameters of ATX interaction with Aβ1-42. Methods: For this purpose, Aβ1-42 was immobilized on the activated surface plasmon resonance (SPR) gold chip surface and then ATX at various concentrations (1-25 μM) was injected with flow rate 30 μl/min for 2 min. The values of arbitrary response unit (RU) were determined at four different temperatures. The dissociation (kd) and association (ka) rate constants were calculated using the SPR Navi™ Data viewer and Trace Drawer™ Software. The Gibbs energy change (ΔG°), enthalpy change (ΔH°), and entropy change (ΔS°) were estimated from van’t Hoff analysis. Results: The negative values of ΔH° (-165.72 kJ mol−1) and ΔS° (-658.63 J mol−1 K-1) suggested that the hydrogen bonds and van der waals interactions were the main forces governing Aβ1-42/ATX interaction. The SPR results also showed that the binding of ATX to Aβ1-42 is a non-spontaneous, exothermic and enthalpy-driven process with KD= 0.31 × 10-6 M at 310 K. Furthermore, the docking of Aβ1-42 structures (PDB IDs: 1IYT, 1Z0Q, and 5OQV) with ATX (extracted from PDB ID: 1GKA) were performed using AutoDock Vina and LigPlot+ molecular docking software. The docking results revealed that hydrophobic and hydrogen bond forces have an important role in the interaction of Aβ1–42 with ATX. Conclusion: Overall, Aβ1–42 seems to have high affinity with ATX and this binding is temperature-independent over the temperature range (298-310 K).

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