Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Adv Protein Chem Struct Biol. 2024;139:405-467. doi: 10.1016/bs.apcsb.2023.11.005. Epub 2024 Feb 15.
This study presents a strategy for extracting significant gene complexes and then provides prospective therapeutics for AD. In this research, a total of 7905 reports published from 1981 to 2022 were retrieved. Following a review of all those articles, only the genetic association studies on AD were considered. Finally, there is a list of 453 Alzheimer-related genes in our dataset for network analysis. To this end, an experimentally derived protein-protein interaction (PPI) network from the String database was utilized to extract four meaningful gene complexes functionally interconnected using Cytoscape v3.9.1 software. The acquired gene complexes were subjected to an enrichment analysis using the ClueGO v2.5.9 tool to emphasize the most significant biological processes and pathways. Afterward, extracted gene complexes were used to extract the drugs related to AD from DGI v3.0 database and introduce some new drugs which may be helpful for this disease. Finally, a comprehensive network that included every gene connected to each gene complex group as well as the drug targets for each gene has been shown. Moreover, molecular docking studies have been performed with the selected compounds to identify the interaction pattern with the respective targets. Finally, we proposed a list of 62 compounds as multi-targeted directed drug-like compounds with a degree value between 2 and 5 and 30 compounds as target-specific drug-like compounds, which have not been proclaimed as AD-related drugs in prior scientific and medical investigations. Then, new drugs were suggested that can be experimentally examined for future work. In addition to this, four bipartite networks representing each group's genes and target miRNAs were established to introduce target miRNAs by using the miRWalk v3 server.
本研究提出了一种提取重要基因复合物的策略，为 AD 提供了有前景的治疗方法。在这项研究中，共检索到 1981 年至 2022 年发表的 7905 篇报告。在对所有这些文章进行审查后，仅考虑了与 AD 相关的遗传关联研究。最后，我们的数据集中有 453 个与阿尔茨海默病相关的基因，用于网络分析。为此，我们使用 String 数据库中的实验衍生的蛋白质-蛋白质相互作用 (PPI) 网络，使用 Cytoscape v3.9.1 软件提取四个功能上相互关联的有意义的基因复合物。使用 ClueGO v2.5.9 工具对获得的基因复合物进行富集分析，强调最显著的生物过程和途径。然后，从 DGI v3.0 数据库中提取与 AD 相关的药物，并引入一些可能对这种疾病有帮助的新药。最后，展示了一个综合网络，其中包括与每个基因复合物组相关的每个基因以及每个基因的药物靶点。此外，还对选定的化合物进行了分子对接研究，以确定与各自靶点的相互作用模式。最后，我们提出了一份包含 62 种化合物的清单，这些化合物是具有 2 到 5 度值的多靶定向药物样化合物，以及 30 种作为靶标特异性药物样化合物的化合物，这些化合物在之前的科学和医学研究中尚未被宣布为与 AD 相关的药物。然后，建议了一些新药，可以在未来的工作中进行实验检验。此外，还建立了四个代表每个组的基因和靶标 miRNA 的二分网络，使用 miRWalk v3 服务器引入靶标 miRNA。
