Salemi Michele, Cosentino Filomena, Lanza Giuseppe, Cantone Mariagiovanna, Salluzzo Maria Grazia, Giurato Giorgio, Borgione Eugenia, Marchese Giovanna, Santa Paola Sandro, Lanuzza Bartolo, Romano Corrado, Ferri Raffaele
Oasi Research Institute-IRCCS, Troina, Italy.
Department of Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy.
Arch Med Sci. 2021 Mar 28;19(3):678-686. doi: 10.5114/aoms/131629. eCollection 2023.
Parkinson's disease (PD) is a common adult-onset neurodegenerative disorder caused by a progressive loss of dopaminergic neurons due to the accumulation of α-synuclein in the substantia nigra. Mitochondria are known to play a key role in cell respiratory function and bioenergetics. Indeed, mitochondrial dysfunction causes insufficient energy production required to satisfy the needs of several organs, especially the nervous system. However, the profiling of messenger RNA (mRNA) expression of mitochondrial subunits in PD has not been systematically investigated yet.
We explored the mRNA expression of mitochondrial DNA (mtDNA) encoded respiratory chain (RC) subunits in 43 PD patients and 43 normal controls (NC). Next generation sequencing analysis (NGS) was used and quantitative real-time polymerase chain reaction (qRT-PCR) assay was used for confirmation of the NGS results.
All tested mitochondrial RC subunits were significantly over-expressed in subjects with PD compared to NC. In qRT-PCR the mean expression of all mitochondrial subunits had an expression level of at least 7 times compared to NC.
The over-expression of mitochondrial subunits in PD subjects with respect to NC might be secondary to a degeneration-related alteration of the mitochondrial structure and/or dynamics, or to the occurrence of a compensatory mechanism. The study of specific mRNA by peripheral blood mononuclear cells may provide a further diagnostic frame for early detection PD patients.
帕金森病(PD)是一种常见的成人起病的神经退行性疾病,由黑质中α-突触核蛋白的积累导致多巴胺能神经元逐渐丧失所致。已知线粒体在细胞呼吸功能和生物能量学中起关键作用。事实上,线粒体功能障碍会导致能量产生不足,无法满足多个器官,尤其是神经系统的需求。然而,帕金森病中线粒体亚基的信使核糖核酸(mRNA)表达谱尚未得到系统研究。
我们探究了43例帕金森病患者和43例正常对照(NC)中线粒体DNA(mtDNA)编码的呼吸链(RC)亚基的mRNA表达。采用下一代测序分析(NGS),并使用定量实时聚合酶链反应(qRT-PCR)检测来确认NGS结果。
与正常对照相比,所有检测的线粒体呼吸链亚基在帕金森病患者中均显著过度表达。在qRT-PCR中,所有线粒体亚基的平均表达水平与正常对照相比至少高出7倍。
帕金森病患者相对于正常对照线粒体亚基的过度表达可能继发于线粒体结构和/或动力学的退变相关改变,或继发于代偿机制的出现。通过外周血单个核细胞研究特定mRNA可能为早期检测帕金森病患者提供进一步的诊断框架。