Genome-wide gene expression data for cell model of Parkinson's disease (PD) have considerably improved our understanding of the underlying molecular mechanisms involved in cell death during PD neurodegeneration. Apomorphine (APOM), a nonselective dopamine agonist, has been used to treat patients with advanced PD showing no response to levodopa or other dopamine agonists. Although APOM plays a role as a free radical scavenger with neuroprotective effect, it has been reported that long-term use of APOM in PD treatment brings about side effects such as nausea and orthostatic hypotension. For safe use of APOM in PD treatment, it is crucial to understand the underlying molecular mechanisms of APOM in PD. In this study, two groups of microarray data including PD cell model and APOM added PD cell model were used to survey mediation effects of APOM in PD cell model. Mediation analysis between disease genes obtained from PD cell model and drug genes obtained from APOM added PD cell model was carried out with shortest path model on KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways and partial least squares structure equation modeling. Our results suggest that drug genes responding to APOM might contribute to negative regulation of disease genes by direct or indirect ways.

中文翻译：

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使用偏最小二乘结构方程模型分析帕金森病细胞模型中阿扑吗啡介导的效应。

帕金森病 (PD) 细胞模型的全基因组基因表达数据大大提高了我们对 PD 神经变性过程中细胞死亡的潜在分子机制的理解。阿扑吗啡 (APOM) 是一种非选择性多巴胺激动剂，已用于治疗对左旋多巴或其他多巴胺激动剂无反应的晚期 PD 患者。虽然APOM起到了自由基清除剂的作用，具有神经保护作用，但有报道称，长期使用APOM治疗PD会带来恶心、体位性低血压等副作用。为了在 PD 治疗中安全使用 APOM，了解 APOM 在 PD 中的潜在分子机制至关重要。在这项研究中，采用PD细胞模型和APOM添加PD细胞模型两组微阵列数据，考察APOM在PD细胞模型中的中介作用。使用KEGG（京都基因与基因组百科全书）路径上的最短路径模型和偏最小二乘结构方程建模，对PD细胞模型获得的疾病基因与APOM添加的PD细胞模型获得的药物基因进行中介分析。我们的结果表明，响应 APOM 的药物基因可能通过直接或间接的方式对疾病基因的负调控做出贡献。