Interaction of donepezil with tau protein: Insights from surface plasmon resonance and molecular modeling methods

Abstract

Introduction: Alzheimer's is a progressive neurodegenerative disease in which extracellular precipitation of amyloid fibrils of the β peptides and the accumulation of phosphorylated tau in neurofibrillary tangles play major roles. There is some indirect evidence indicating the potential of donepezil to interact with tau protein. There is no published data investigating the binding interaction of donepezil with tau protein. in the present study, the kinetics and thermodynamics of donepezil binding to tau protein have been evaluated using surface plasmon resonance (SPR) technique. Aim: In this research work, the study of interaction of donepezil with tau protein was investigated and the study of donepezil interaction with tau protein could be helpful in understanding the donepezil mechanism of action in AD and designing and developing more effective anti-Alzheimer’s drug. Materials and Methods: In the present study, various aspects of donepezil binding to tau protein have been investigated using surface plasmon resonance tau protein was immobilized on Au chip using 11-mercaptoundecanoic acid (MUA) and the interaction of various concentrations of donepezil with the immobilized tau was evaluated by SPR at different temperatures. Results & Discussion: Tau protein binding study with donepezil was performed using SPR. donepezil molecule affinity to tau was increased, which was confirmed by decreasing values of KD upon rising temperature. Conclusion: The calculated thermodynamic parameters showed that the main force involved in the interaction is van der Waals and hydrogen bonding. value of ΔG demonstrated that the binding reaction was not thermodynamically favorable and the nature of the binding between donepezil and tau protein is not spontaneous.