title: Identification of potential drugs for Parkinson's disease based on a sub-pathway method.
abstract: 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.
authors.affiliation: a Department of Neurology , The First Affiliated Hospital of Harbin Medical University , Harbin , P. R. China.
authors.forename: Ai-Guo
authors.initials: AG
authors.lastname: Sun
authors.affiliation: a Department of Neurology , The First Affiliated Hospital of Harbin Medical University , Harbin , P. R. China.
authors.forename: Ai-Qi
authors.initials: AQ
authors.lastname: Lin
authors.affiliation: a Department of Neurology , The First Affiliated Hospital of Harbin Medical University , Harbin , P. R. China.
authors.forename: Shao-Yue
authors.initials: SY
authors.lastname: Huang
authors.affiliation: a Department of Neurology , The First Affiliated Hospital of Harbin Medical University , Harbin , P. R. China.
authors.forename: Di
authors.initials: D
authors.lastname: Huo
authors.affiliation: a Department of Neurology , The First Affiliated Hospital of Harbin Medical University , Harbin , P. R. China.
authors.forename: Chao-Hua
authors.initials: CH
authors.lastname: Cong
mesh_terms: D016022:Case-Control Studies; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D015870:Gene Expression; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
keywords: Parkinson's disease; drugs; sub-pathway