National Research Center "Kurchatov Institute", Moscow, 123182, Russia.
Biochemistry (Mosc). 2023 Apr;88(4):515-525. doi: 10.1134/S0006297923040077.
Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. Despite numerous studies, the causes of this pathology remain completely unknown. This is, among other things, due to the difficulty of obtaining biological material for analysis. Neural cell cultures derived from the induced pluripotent stem cells (IPSCs) provide a great potential for studying molecular events underlying the pathogenesis of PD. This paper presents the results of bioinformatic analysis of the data obtained using RNA-seq technology in the study of neural precursors (NP) derived from IPSCs of the healthy donors and patients with PD carrying various mutations that are commonly associated with familial PD. This analysis showed that the level of transcription of multiple genes actively expressed in the nervous system at the embryonic stage of development was significantly increased in the NP cells obtained from the patients with PD, unlike in the case of healthy donors. Bioinformatic data have been, in general, confirmed using real-time PCR. The obtained data suggest that one of the causes of PD may be the shift of the gene expression pattern in neuronal cells towards embryonic gene expression pattern (termed dematuration).
帕金森病(PD)是世界上最常见的神经退行性疾病之一。尽管进行了大量研究,但这种病理学的原因仍然完全未知。这在一定程度上是由于难以获得用于分析的生物材料。源自诱导多能干细胞(iPSCs)的神经细胞培养物为研究 PD 发病机制的分子事件提供了巨大的潜力。本文介绍了使用 RNA-seq 技术在研究源自健康供体和携带与家族性 PD 相关的各种突变的 PD 患者的 iPSCs 的神经前体细胞(NP)中获得的数据进行生物信息学分析的结果。该分析表明,与健康供体相比,源自 PD 患者的 NP 细胞中,多个在胚胎发育阶段神经系统中活跃表达的基因的转录水平显著升高。生物信息学数据已使用实时 PCR 进行了总体验证。所得数据表明,PD 的一个原因可能是神经元细胞中的基因表达模式向胚胎基因表达模式(称为去成熟)的转变。