Sun Ai-Guo, Lin Ai-Qi, Huang Shao-Yue, Huo Di, Cong Chao-Hua
a Department of Neurology , The First Affiliated Hospital of Harbin Medical University , Harbin , P. R. China.
Int J Neurosci. 2016;126(4):318-25. doi: 10.3109/00207454.2014.986673. Epub 2015 Sep 24.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease in ageing individuals. Current therapeutic regimen suffers from general side effects and a poor efficiency for PD symptoms. The need for development new therapeutic agents for PD is urgent. Here, we aimed to explore the metabolic mechanism of PD and identified potential novel agents for PD by a sub-pathway-based method. By using the GSE7621 microarray data from the GEO database, we first identified the 1226 differentially expressed genes (DEGs) between PD and normal samples. Then we identified 19 significant enriched metabolic sub-pathways, which may involve in development of PD. Finally, by an integrated analysis of PD-involved sub-pathways and drug-affected sub-pathways, we identified 49 novel small molecular drugs capable to target the PD-involved sub-pathways. Our method could not only identify existing drug (apomorphine) for PD, but also predict potentially novel agents (ketoconazole and astemizole), which might have therapeutic effects via targeting some key enzymes in arachidonic acid metabolism. These candidate agents identified by our approach may provide insights into a novel therapy approach for PD.
帕金森病（PD）是老年人群中第二常见的神经退行性疾病。目前的治疗方案存在普遍的副作用，且对帕金森病症状的治疗效果不佳。迫切需要开发针对帕金森病的新型治疗药物。在此，我们旨在探索帕金森病的代谢机制，并通过基于子通路的方法鉴定帕金森病的潜在新型药物。通过使用来自基因表达综合数据库（GEO）的GSE7621芯片数据，我们首先鉴定出帕金森病样本与正常样本之间的1226个差异表达基因（DEGs）。然后我们鉴定出19条显著富集的代谢子通路，这些子通路可能与帕金森病的发生发展有关。最后，通过对与帕金森病相关的子通路和药物作用的子通路进行综合分析，我们鉴定出49种能够靶向与帕金森病相关子通路的新型小分子药物。我们的方法不仅能够鉴定出针对帕金森病的现有药物（阿扑吗啡），还能预测潜在的新型药物（酮康唑和阿司咪唑），它们可能通过靶向花生四烯酸代谢中的一些关键酶而具有治疗作用。通过我们的方法鉴定出的这些候选药物可能为帕金森病的新型治疗方法提供思路。
