Abstract
Tau, as a small protein in neurons, plays a main role in stabilizing and assembling the internal microtubules. Here, the effects of antiepileptic drugs, including lamotrigine (LTG) and phenobarbital (PHB), on tau protein structure have been investigated by surface plasmon resonance (SPR), fluorescence spectroscopy along molecular modeling. Fluorescence data analysis revealed that both drugs quench the intrinsic emission intensity of tau protein via a static quenching mechanism. Analysis of SPR data at three different temperatures revealed that binding of LTG and PHB to tau protein leads to a decrease and increase in equilibrium constants (K(D)) values with increasing temperature, respectively. Therefore, the affinity of LTG decreases and PHB increases with increasing temperature. In addition, molecular docking studies indicated that both LTG and PHB bind to the S1 pocket of tau protein. Our data demonstrated the preventive effect of two important antiepileptic pharmaceuticals on the aggregation of tau protein. Given that any damage to the tau protein possibly leads to neurodegenerative diseases, this study can provide useful and important information and a basis for further research and study to treat tauopathy.