Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Research Center of Neurology, 125367 Moscow, Russia.
Biomolecules. 2022 Mar 24;12(4):493. doi: 10.3390/biom12040493.
Parkinson disease (PD) is attributed to a proteostasis disorder mediated by α-synuclein accumulating in a specific brain region. PD manifestation is often related to extraneuronal alterations, some of which could be used as diagnostic or prognostic PD biomarkers. In this work, we studied the shifts in the expression of proteostasis-associated chaperones of the HSP70 family and autophagy-dependent p62 protein values in the peripheral blood mononuclear cells (PBMC) of mild to moderate PD patients. Although we did not detect any changes in the intracellular HSP70 protein pool in PD patients compared to non-PD controls, an increase in the transcriptional activity of the stress-associated and genes was observed in these cells. Basal p62 content was found to be increased in PD patients' PBMC, similarly to the p62 level in substantia nigra neural cells in PD. Moreover, the spontaneous apoptosis level was increased among PBMC and positively correlated with the p62 intracellular level in the PD group. A combined - and p62-based analysis among 26 PD patients and 36 age-matched non-PD controls pointed out the diagnostic significance of these markers, with intermediate sensitivity and high specificity of this combination when observing patients diagnosed with PD.
帕金森病（PD）归因于由在特定脑区域积累的α-突触核蛋白介导的蛋白质稳态紊乱。PD 的表现通常与细胞外改变有关，其中一些可作为诊断或预测 PD 的生物标志物。在这项工作中，我们研究了轻度至中度 PD 患者外周血单个核细胞（PBMC）中与蛋白质稳态相关的热休克蛋白 70 家族伴侣和自噬依赖性 p62 蛋白值的表达变化。尽管与非 PD 对照组相比，我们未在 PD 患者的细胞内 HSP70 蛋白库中检测到任何变化，但这些细胞中应激相关的 和 基因的转录活性增加。在 PD 患者的 PBMC 中发现基础 p62 含量增加，与 PD 患者黑质神经元细胞中的 p62 水平相似。此外，PBMC 中的自发性细胞凋亡水平增加，并与 PD 组中 p62 的细胞内水平呈正相关。对 26 名 PD 患者和 36 名年龄匹配的非 PD 对照组进行的 -和 p62 联合分析表明了这些标志物的诊断意义，当观察到被诊断为 PD 的患者时，该组合具有中等敏感性和高特异性。
