Sharo Catherine, Zhai Tianhua, Huang Zuyi
Department of Chemical and Biological Engineering, Villanova University, Villanova, PA 19085, USA.
Pharmaceuticals (Basel). 2024 Jan 20;17(1):137. doi: 10.3390/ph17010137.
Alzheimer's disease has become a major public health issue. While extensive research has been conducted in the last few decades, few drugs have been approved by the FDA to treat Alzheimer's disease. There is still an urgent need for understanding the disease pathogenesis, as well as identifying new drug targets for further drug discovery. Alzheimer's disease is known to arise from a build-up of amyloid beta (Aβ) plaques as well as tangles of tau proteins. Along similar lines to Alzheimer's disease, inflammation in the brain is known to stem from the degeneration of tissue and build-up of insoluble materials. A minireview was conducted in this work assessing the genes, proteins, reactions, and pathways that link brain inflammation and Alzheimer's disease. Existing tools in Systems Biology were implemented to build protein interaction networks, mainly for the classical complement pathway and G protein-coupled receptors (GPCRs), to rank the protein targets according to their interactions. The top 10 protein targets were mainly from the classical complement pathway. With the consideration of existing clinical trials and crystal structures, proteins C5AR1 and GARBG1 were identified as the best targets for further drug discovery, through computational approaches like ligand-protein docking techniques.
阿尔茨海默病已成为一个重大的公共卫生问题。尽管在过去几十年里进行了广泛的研究，但美国食品药品监督管理局（FDA）批准用于治疗阿尔茨海默病的药物却寥寥无几。目前仍迫切需要了解该疾病的发病机制，并确定新的药物靶点以进一步开展药物研发。众所周知，阿尔茨海默病是由β-淀粉样蛋白（Aβ）斑块的积累以及tau蛋白缠结引起的。与阿尔茨海默病类似，已知大脑中的炎症源于组织退化和不溶性物质的积累。这项工作进行了一项小型综述，评估了将大脑炎症与阿尔茨海默病联系起来的基因、蛋白质、反应和途径。利用系统生物学中的现有工具构建了蛋白质相互作用网络，主要针对经典补体途径和G蛋白偶联受体（GPCR），根据它们的相互作用对蛋白质靶点进行排名。排名前十的蛋白质靶点主要来自经典补体途径。考虑到现有的临床试验和晶体结构，通过配体-蛋白质对接技术等计算方法，确定蛋白质C5AR1和GARBG1为进一步药物研发的最佳靶点。
