Midbrain dopamine neurons in Parkinson's disease exhibit a dysregulated miRNA and target-gene network.
Midbrain dopamine neurons in Parkinson's disease exhibit a dysregulated miRNA and target-gene network.
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DOI：
10.1016/j.brainres.2015.05.021
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发表时间：
2015-08-27
期刊：
影响因子：
2.9
通讯作者：
Sonntag KC
中科院分区：
文献类型：
--
作者：
Briggs CE;Wang Y;Kong B;Woo TU;Iyer LK;Sonntag KC
散发性帕金森病（PD）黑质（SN）多巴胺（DA）神经元的变性以基因表达网络紊乱为特征。微RNA是基因表达的转录后调节因子，我们最近提供的证据表明，这些分子可能在PD的发病机制中发挥功能性作用。在这里，我们记录了SN DA神经元和PD中miRNA的全面分析，包括性别差异。我们的数据显示，miRNAs在受疾病影响的神经元中失调，并且在男性和女性样本之间差异表达，男性中更多的上调miRNAs和女性中更多的下调miRNAs。无偏的免疫抑制通路分析（IPA）揭示了一个miRNA/靶基因关联的网络，这与PD病理学中功能失调的基因和信号通路一致。我们的研究提供了证据表明，miRNA与SN DA神经元的细胞功能和身份，以及与PD发病机制相关的失调基因表达网络和信号通路可能具有性别特异性。
The degeneration of substantia nigra (SN) dopamine (DA) neurons in sporadic Parkinson’s disease (PD) is characterized by disturbed gene expression networks. Micro(mi)RNAs are post-transcriptional regulators of gene expression and we recently provided evidence that these molecules may play a functional role in the pathogenesis of PD. Here, we document a comprehensive analysis of miRNAs in SN DA neurons and PD, including sex differences. Our data show that miRNAs are dysregulated in disease-affected neurons and differentially expressed between male and female samples with a trend of more up-regulated miRNAs in males and more down-regulated miRNAs in females. Unbiased Ingenuity Pathway Analysis (IPA) revealed a network of miRNA/target-gene associations that is consistent with dysfunctional gene and signaling pathways in PD pathology. Our study provides evidence for a general association of miRNAs with the cellular function and identity of SN DA neurons, and with deregulated gene expression networks and signaling pathways related to PD pathogenesis that may be sex-specific.