PDF(Pubmed)
Abstract：
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.
摘要：
阿尔茨海默病已经成为一个重大的公共卫生问题。虽然在过去的几十年中进行了广泛的研究，很少有药物被FDA批准用于治疗阿尔茨海默病。目前仍迫切需要了解该病的发病机制,以及确定新的药物靶标以进一步发现药物。已知阿尔茨海默氏病是由β淀粉样蛋白（Aβ）斑块的积累以及tau蛋白的缠结引起的。与阿尔茨海默病相似，众所周知，大脑中的炎症源于组织的退化和不溶性物质的积累。在这项评估基因的工作中进行了简短的回顾，蛋白质，reactions,和连接大脑炎症和阿尔茨海默病的途径。系统生物学中现有的工具被用来构建蛋白质相互作用网络，主要用于经典补体途径和G蛋白偶联受体（GPCRs），根据它们的相互作用对蛋白质靶标进行排序。前10个蛋白质靶标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，蛋白质C5AR1和GARBG1被确定为进一步药物发现的最佳靶标，通过计算方法，如配体-蛋白质对接技术。
