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


UZUNHİSARCIKLI E., ÇELİK İ., Yerer M. B.

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, cilt.42, sa.1, ss.384-392, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 42 Sayı: 1
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1080/07391102.2023.2192806
  • Dergi Adı: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core
  • Sayfa Sayıları: ss.384-392
  • Anahtar Kelimeler: Tau, molecular docking, GSK-3 beta inhibitors, neurodegeneration, molecular dynamics simulation
  • Erciyes Üniversitesi Adresli: Evet

Özet

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-3b (GSK-3b), which is one of the tau kinases, the effectiveness of potential GSK-3b 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-3b 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-3b and reduces the level of phosphorylated tau. In summary, our findings suggested Neomangiferin can be a therapeutic candidate for AD treatment.