Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Department of Neurology, Yongin Severance Hospital, Yonsei University Health System, Yongin, Korea.
Yonsei Med J. 2022 Aug;63(8):724-734. doi: 10.3349/ymj.2022.63.8.724.
Hereditary parkinsonism genes consist of causative genes of familial Parkinson's disease (PD) with a locus symbol prefix ( genes) and hereditary atypical parkinsonian disorders that present atypical features and limited responsiveness to levodopa (non- genes). Although studies have shown that hereditary parkinsonism genes are related to idiopathic PD at the phenotypic, gene expression, and genomic levels, no study has systematically investigated connectivity among the proteins encoded by these genes at the protein-protein interaction (PPI) level.
Topological measurements and physical interaction enrichment were performed to assess PPI networks constructed using some or all the proteins encoded by hereditary parkinsonism genes (n=96), which were curated using the Online Mendelian Inheritance in Man database and literature.
Non- and genes were involved in common functional modules related to autophagy, mitochondrial or lysosomal organization, catecholamine metabolic process, chemical synapse transmission, response to oxidative stress, neuronal apoptosis, regulation of cellular protein catabolic process, and vesicle-mediated transport in synapse. The hereditary parkinsonism proteins formed a single large network comprising 51 nodes, 83 edges, and three PPI pairs. The probability of degree distribution followed a power-law scaling behavior, with a degree exponent of 1.24 and a correlation coefficient of 0.92. was identified as a hub gene with the highest degree of betweenness centrality; its physical interaction enrichment score was 1.28, which was highly significant.
Both and non- genes show high connectivity at the PPI and biological functional levels.
遗传性帕金森病基因包括具有基因座符号前缀（基因）的家族性帕金森病（PD）的致病基因和表现出非典型特征且对左旋多巴反应有限的遗传性非典型帕金森病（非基因）。尽管研究表明遗传性帕金森病基因在表型、基因表达和基因组水平上与特发性 PD 有关，但尚无研究系统地研究这些基因编码的蛋白质之间在蛋白质-蛋白质相互作用（PPI）水平上的连接。
采用拓扑测量和物理相互作用富集方法，评估使用遗传性帕金森病基因（n=96）中部分或全部编码蛋白构建的 PPI 网络，这些基因使用在线孟德尔遗传数据库和文献进行了策展。
非基因和基因参与与自噬、线粒体或溶酶体组织、儿茶酚胺代谢过程、化学突触传递、氧化应激反应、神经元凋亡、细胞蛋白分解代谢过程调节和突触中囊泡介导的运输相关的常见功能模块。遗传性帕金森病蛋白形成了一个由 51 个节点、83 个边和 3 个 PPI 对组成的单一大型网络。度分布的概率遵循幂律分布行为，度指数为 1.24，相关系数为 0.92。被鉴定为具有最高介数中心度的枢纽基因；其物理相互作用富集评分为 1.28，具有高度显著性。
基因和非基因在 PPI 和生物学功能水平上均显示出高度的连通性。
