Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology and Biodiversity Research Institute (IRBio), Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain.
Mind the Byte S.L., 08007 Barcelona, Catalonia, Spain.
Mar Drugs. 2018 Oct 16;16(10):386. doi: 10.3390/md16100386.
Alzheimer's disease (AD) is becoming one of the most disturbing health and socioeconomic problems nowadays, as it is a neurodegenerative pathology with no treatment, which is expected to grow further due to population ageing. Actual treatments for AD produce only a modest amelioration of symptoms, although there is a constant ongoing research of new therapeutic strategies oriented to improve the amelioration of the symptoms, and even to completely cure the disease. A principal feature of AD is the presence of neurofibrillary tangles (NFT) induced by the aberrant phosphorylation of the microtubule-associated protein tau in the brains of affected individuals. Glycogen synthetase kinase-3 beta (GSK3β), casein kinase 1 delta (CK1δ), dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) and dual-specificity kinase cdc2-like kinase 1 (CLK1) have been identified as the principal proteins involved in this process. Due to this, the inhibition of these kinases has been proposed as a plausible therapeutic strategy to fight AD. In this study, we tested in silico the inhibitory activity of different marine natural compounds, as well as newly-designed molecules from some of them, over the mentioned protein kinases, finding some new possible inhibitors with potential therapeutic application.
阿尔茨海默病（AD）正成为当今最令人不安的健康和社会经济问题之一，因为它是一种没有治疗方法的神经退行性病理学，由于人口老龄化，预计这一问题还会进一步恶化。目前针对 AD 的治疗方法只能适度改善症状，尽管人们一直在不断研究新的治疗策略，旨在改善症状的改善，甚至完全治愈这种疾病。AD 的一个主要特征是在受影响个体的大脑中微管相关蛋白 tau 的异常磷酸化诱导的神经原纤维缠结（NFT）的存在。糖原合酶激酶 3β（GSK3β）、酪蛋白激酶 1 德尔塔（CK1δ）、双特异性酪氨酸磷酸化调节激酶 1A（DYRK1A）和双特异性激酶 cdc2 样激酶 1（CLK1）已被确定为参与该过程的主要蛋白质。因此，抑制这些激酶已被提议作为治疗 AD 的一种合理的治疗策略。在这项研究中，我们通过计算机模拟测试了不同海洋天然化合物以及其中一些新设计分子对上述蛋白激酶的抑制活性，发现了一些具有潜在治疗应用的新的可能抑制剂。
