Laboratory of Neural and Neuroendocrine Regulations, Koltzov Institute of Developmental Biology of the Russian Academy of Sciences, 119334 Moscow, Russia.
Genes (Basel). 2023 Dec 12;14(12):2202. doi: 10.3390/genes14122202.
Studying the molecular mechanisms of the pathogenesis of Parkinson's disease (PD) is critical to improve PD treatment. We used OpenArray technology to assess gene expression in the substantia nigra (SN) cells of mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and in controls. Among the 11 housekeeping genes tested, was taken as the reference gene due to its most stable expression in normal and experimental conditions. From 101 genes encoding functionally significant proteins of nigrostriatal dopaminergic neurons, 57 highly expressed genes were selected to assess their expressions in the PD model and in the controls. The expressions of , , , , , , , and decreased in the experiment compared to the control, indicating decreases in the synthesis, degradation, and transport of dopamine and the impaired autoregulation of dopaminergic neurons. The expressions of , , , , , , , , , , , and genes were also decreased in the MPTP-treated mice, indicating impairments of axonal and vesicular transport and abnormal functioning of the antioxidant and ubiquitin-proteasome systems in the SN. The detected decreases in the expressions of , , , and may serve to reduce pathological protein aggregation, increase dopamine release in the striatum, prevent mitophagy, and restore the redox status of SN cells.
研究帕金森病 (PD) 发病机制的分子机制对于改善 PD 治疗至关重要。我们使用 OpenArray 技术评估了 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的 PD 模型和对照组小鼠黑质 (SN) 细胞中的基因表达。在测试的 11 个管家基因中, 由于其在正常和实验条件下表达最稳定,因此被选为参考基因。从编码黑质纹状体多巴胺能神经元功能重要蛋白的 101 个基因中,选择了 57 个高表达基因来评估它们在 PD 模型和对照组中的表达。与对照组相比, 、 、 、 、 、 、 和 基因的表达在实验中减少,表明多巴胺的合成、降解和转运减少,以及多巴胺能神经元的自身调节受损。 、 、 、 、 、 、 、 、 、 和 基因在 MPTP 处理的小鼠中也减少,表明轴突和囊泡运输受损以及 SN 中的抗氧化和泛素蛋白酶体系统异常。检测到的 、 、 和 基因表达减少可能有助于减少病理性蛋白聚集、增加纹状体多巴胺释放、防止线粒体自噬和恢复 SN 细胞的氧化还原状态。