Department of Pharmacology, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.
J Biomol Struct Dyn. 2024 Jan-Feb;42(1):384-392. doi: 10.1080/07391102.2023.2192806. Epub 2023 Mar 22.
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 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.
在阿尔茨海默病（AD）中，神经原纤维缠结由过度磷酸化的 tau 蛋白组成，tau 过度磷酸化会降低微管结合能力。许多蛋白激酶被认为参与了 tau 的过度磷酸化。基于 tau 过度磷酸化可以通过抑制糖原合酶激酶-3β（GSK-3β）来预防这一事实，GSK-3β 是 tau 激酶之一，因此通过虚拟筛选、分子对接和动力学模拟研究阿尔茨海默病发病机制来检验潜在 GSK-3β 抑制剂的有效性，并通过研究来探讨其在神经退行性变中的作用。根据在神经元分化研究中建立的阿尔茨海默病模型中通过虚拟筛选和分子对接确定的潜在化合物的研究结果，新芒果苷被确定为最有效的分子。MTT 法和实时细胞分析显示，新芒果苷具有诱导神经退行性变的保护作用。已确定新芒果苷抑制 GSK-3β 并降低磷酸化 tau 水平。总之，我们的研究结果表明，新芒果苷可能是治疗 AD 的候选药物。Ramaswamy H. Sarma 通讯。
