Detection of natural compounds by virtual screening, molecular docking and dynamics studies and evaluation of their effects on tau level in vitro Alzheimer’s model

Abstract

In Alzheimer’s disease (AD), neurofibrillary tangles are composed of hyperphosphorylated tau protein, and tau hyperphosphorylation reduces microtubule binding. Many protein kinases are thought to be involved in tau hyperphosphorylation. Based on the fact that tau hyperphosphorylation can be prevented by inhibition of glycogen synthase kinase-3β (GSK-3β), which is one of the tau kinases, the effectiveness of potential GSK-3β inhibitors determined by virtual screening, molecular docking, and dynamics simulations studies on Alzheimer’s pathology has been examined and its role in neurodegeneration has been investigated by studies. Neomangiferin was determined as the most effective molecule according to the results of studies with potential compounds determined by virtual screening and molecular docking to be GSK-3β inhibitors in the in vitro Alzheimer’s model created by neuronal differentiation studies. Neomangiferin has been shown to have a protective role in induced neurodegeneration by the MTT method and Real Time Cell Analysis. It has been determined that Neomangiferin inhibits GSK-3β and reduces the level of phosphorylated tau. In summary, our findings suggested Neomangiferin can be a therapeutic candidate for AD treatment.

Communicated by Ramaswamy H. Sarma

Keywords:

• Tau
• molecular docking
• GSK-3β inhibitors
• neurodegeneration
• molecular dynamics simulation

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the Erciyes University Scientific Research Projects Coordination Unit under grant number TKB-2020-10163. The authors thank Ankara University-Scientific Research Unity for supplying the Schrödinger software purchased under grant project number BAP-21B0237004. The molecular dynamics calculations reported in this paper were partially performed at TUBITAK ULAKBIM in TURKEY, High Performance and Grid Computing Center (TRUBA resources).