Vargas-Medrano Javier, Yang Barbara, Garza Nathan T, Segura-Ulate Ismael, Perez Ruth G
Department of Biomedical Sciences, Center of Emphasis in Neurosciences, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX 79905, USA.
Department of Biomedical Sciences, Center of Emphasis in Neurosciences, Texas Tech University Health Sciences Center El Paso, Paul L. Foster School of Medicine, El Paso, TX 79905, USA.
Neurosci Lett. 2019 Jan 18;690:178-180. doi: 10.1016/j.neulet.2018.10.040. Epub 2018 Oct 22.
In searching for Parkinson's disease (PD) pharmacotherapies we began studying FTY720, a food and drug administration (FDA) approved drug. We also created derivatives, FTY720-C2 and FTY720-Mitoxy, and began assessing them. Here we treated dopaminergic MN9D cells with FTY720s then measured microRNA (miRNA) levels by PCR arrays. We discovered that all three FTY720s increased miR376b-3p, while FTY720-C2 also increased miR-128-3p, miR-146b-5p, miR-7a-5p, and miR-9-5p, and FTY720-Mitoxy also increased miR-30d-5p. Investigations revealed that some miRNAs downregulate alpha-synuclein, while others reduce apoptosis, suggesting that FTY720s may act to reduce synucleinopathy and dopaminergic neuron loss in PD and related disorders.
在寻找帕金森病（PD）药物疗法的过程中，我们开始研究FTY720，一种已获美国食品药品监督管理局（FDA）批准的药物。我们还制备了衍生物FTY720-C2和FTY720-Mitoxy，并开始对它们进行评估。在此，我们用FTY720s处理多巴胺能MN9D细胞，然后通过PCR阵列检测微小RNA（miRNA）水平。我们发现，所有三种FTY720s均能增加miR376b-3p的水平，而FTY720-C2还能增加miR-128-3p、miR-146b-5p、miR-7a-5p和miR-9-5p的水平，FTY720-Mitoxy也能增加miR-30d-5p的水平。研究表明，一些miRNA可下调α-突触核蛋白，而另一些则可减少细胞凋亡，这表明FTY720s可能有助于减轻PD及相关疾病中的突触核蛋白病和多巴胺能神经元损失。
