Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.

非典型帕金森症（AP）是一组复杂的神经退行性疾病，具有明显的临床和病理生理学异质性。系统生物学工具的使用可能有助于表征中枢瓶颈基因，并确定其生物学途径，以拓宽对这些疾病基础的理解。对 DisGeNET 数据库进行了系统搜索，该数据库整合了来自专家管理的存储库、GWAS 目录、动物模型和科学文献的数据。使用工具 STRING 11.0 和 Cytoscape 3.8.2 分析蛋白质-蛋白质相互作用 (PPI) 网络。使用 Cytoscape 的 CytoHubba 0.1 插件进行 PPI 网络拓扑分析。将中心基因和瓶颈基因插入 InteractiveVenn 上的 4 个不同组中。进行了额外的功能富集分析，以确定京都基因和基因组百科全书 (KEGG) 途径和一组描述的基因的基因本体。 DisGeNET 数据库中的系统搜索确定了 485 个与非典型帕金森症相关的基因。将这些基因叠加，我们总共检测到了 31 个中枢瓶颈基因。此外，我们的功能富集分析证明了这些中枢瓶颈基因参与了 3 个主要 KEGG 通路。我们通过系统生物学方法鉴定了 31 个高度关联的中枢瓶颈基因，这些基因可能在非典型帕金森病的发病机制中发挥关键作用。功能富集分析表明，这些基因参与了胶质细胞发育、胶质细胞激活和认知等多种生物过程和通路，其中通路与阿尔茨海默病和帕金森病相关。作为一个假设，我们强调 AP 可能的关键基因有MAPT（微管相关蛋白 tau）、APOE（载脂蛋白 E）、SNCA（突触核蛋白 α）和APP（淀粉样蛋白 β 前体蛋白）基因。