Sokolowski Igor, Kucharska-Lusina Aleksandra, Miller Elzbieta, Poplawski Tomasz, Majsterek Ireneusz
Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Mazowiecka 5, 92-215 Lodz, Poland.
Department of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, Poland.
Curr Issues Mol Biol. 2024 Oct 19;46(10):11668-11680. doi: 10.3390/cimb46100693.
Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by immune-mediated inflammation and neurodegeneration in the central nervous system (CNS). In this study; we aimed to investigate the gene expression and plasma protein levels of three neuroprotective genes-heat shock proteins (HSP90 and HSP60) and glial cell line-derived neurotrophic factor (GDNF)-in MS patients compared to healthy controls. Forty patients with relapsing-remitting MS and 40 healthy volunteers participated in this study. Gene expression was measured using reverse transcription quantitative real-time PCR, and protein levels were assessed via ELISA. The results showed a significant increase in (1.7-fold) and (2-fold) gene expression in MS patients compared to controls, along with corresponding increases in protein levels (1.5-fold for both HSP90 and HSP60). In contrast, gene expression and protein levels were significantly reduced in MS patients, with a 7-fold decrease in gene expression and a 1.6-fold reduction in protein levels. Notably, a non-linear relationship between gene expression and protein concentration was observed in MS patients, suggesting complex regulatory mechanisms influencing GDNF in the disease. The upregulation of HSP90 and HSP60 in MS highlights their roles in immune regulation and stress responses, while the reduction in GDNF indicates impaired neuroprotection. These findings suggest that HSP90, HSP60, and GDNF could serve as biomarkers for disease progression and as potential therapeutic targets in MS, offering promising avenues for future research and treatment development.
多发性硬化症(MS)是一种慢性神经退行性疾病,其特征是中枢神经系统(CNS)中存在免疫介导的炎症和神经退行性变。在本研究中,我们旨在调查与健康对照相比,三种神经保护基因——热休克蛋白(HSP90和HSP60)和胶质细胞源性神经营养因子(GDNF)——在MS患者中的基因表达和血浆蛋白水平。40例复发缓解型MS患者和40名健康志愿者参与了本研究。使用逆转录定量实时PCR测量基因表达,并通过ELISA评估蛋白水平。结果显示,与对照组相比,MS患者中HSP90(1.7倍)和HSP60(2倍)的基因表达显著增加,蛋白水平也相应增加(HSP90和HSP60均为1.5倍)。相反,MS患者中GDNF的基因表达和蛋白水平显著降低,基因表达降低7倍,蛋白水平降低1.6倍。值得注意的是,在MS患者中观察到GDNF基因表达与蛋白浓度之间存在非线性关系,这表明在该疾病中影响GDNF的调控机制较为复杂。MS中HSP90和HSP60的上调突出了它们在免疫调节和应激反应中的作用,而GDNF的降低表明神经保护受损。这些发现表明,HSP90、HSP60和GDNF可作为疾病进展的生物标志物以及MS潜在的治疗靶点,为未来的研究和治疗开发提供了有前景的途径。