Effect of Melatonin on Tau aggregation and Tau-mediated cell surface morphology

Abstract

Tau is the major neuronal protein involved in the stabilization of microtubule assembly. In Alzheimers disease, Tau self assembles to form intracellular protein aggregates, which are toxic to cells. Various methods have been tried and tested to restrain the aggregation of Tau. Most of the agents tested for this purpose have limitations in their effectiveness and availability to neuronal cells. We tested melatonin against in vitro Tau aggregation and observed its effect on membrane topology, tubulin network and Tau phosphorylation in neuro2a and N9 cell lines. The aggregation and conformation of Tau was determined by ThT fluorescence and CD spectroscopy respectively. The morphology of Tau aggregates in presence and absence of melatonin was studied by transmission electron microscopy. Melatonin was found to reduce the formation of higher order oligomeric structures without affecting the overall aggregation kinetics of Tau. Melatonin also modulates and helps to maintain membrane topology as evidenced by FE-SEM analysis. Overall, melatonin administration shows mild anti-aggregation and cytoprotective effects.