基于蛋白相互作用网络的帕金森病相关信号通路关键蛋白的筛选

Screening of key proteins in Parkinson's disease-related signaling pathway based on protein-protein in⁃teraction network

目的通过构建帕金森病(PD)信号通路蛋白相互作用网络,探讨PD相关信号通路网络关键蛋白。方法通过文献检索、信号通路数据库、STRING数据库及cytoscape软件,构建PD相关信号通路蛋白相互作用网络。利用cytoscape软件拓扑分析功能寻找信号通路相互作用网络中的关键蛋白。结果共纳入9条PD信号通路,包括PI3K/AKT/mTOR通路、JNK通路、p38 MAPK通路、Wnt/β-catenin通路、Notch通路、SDF-1/CXCR4通路、NF-κB通路、JAK/STAT通路和Nrf2/ARE通路。构建信号通路蛋白相互作用网络后筛选出前10位关键信号蛋白,分别为AKT1、MAPK1、Jun、p53、c-MYC、JNK、TNF、PTEN、STAT3和mTOR。结论成功构建了PD信号通路蛋白相互作用网络,筛选出与PD相关的信号通路蛋白,其中AKT1、MAPK1、Jun、p53、c-MYC、JNK、TNF、PTEN、STAT3、mTOR是PD信号通路蛋白相互作用网络中的关键蛋白,在PD发病过程具有重要作用。

Objective To explore the key proteins of signaling pathways in Parkinson’s disease(PD) by constructing protein-protein interaction(PPI) network.Methods Through literature search,signal pathway database,STRING database and cytoscape software,we constructed a PPI network of PD-related signal pathways.We used the topology analysis function of cytoscape software to find the key proteins in the PPI network of signaling pathways.Results Nine signaling pathways including PI3 K/AKT/mTOR,JNK,p38 MAPK,Wnt/β-catenin,Notch,SDF-1/CXCR4,NF-κB,JAK/STAT and Nrf2/ARE signaling pathways were screened out.The top ten key proteins including AKT1,MAPK1,Jun,p53,c-MYC,JNK,TNF,PTEN,STAT and mTOR were screened out by cytoscape software.Conclusions The PPI network of PD-related signal pathways is successfully established,and the PD-related proteins are screened out.Among them,AKT1,MAPK1,Jun,p53,c-MYC,JNK,TNF,PTEN,STAT3 and mTOR are key proteins in this PPI network,which may play an important role in the pathogenesis of PD.