Impaired age-dependent increases in phosphoglycerate kinase activity in red blood cells of Parkinson's disease patients
Impaired age-dependent increases in phosphoglycerate kinase activity in red blood cells of Parkinson's disease patients
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DOI：
10.1016/j.parkreldis.2021.09.016
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发表时间：
2021-10-01
影响因子：
4.1
通讯作者：
Mizuno, Toshiki
中科院分区：
文献类型：
--
作者：
Fujino, Yuzo;Kasai, Takashi;Mizuno, Toshiki
背景：生物能量学受损部分参与了帕金森病（PD）的发病机制。磷酸甘油酸激酶（PGK）是一种糖酵解的必需酶，近年来因其在PD中的致病作用和作为疾病修饰治疗的靶点而受到关注。本研究旨在评估PD患者和对照组红细胞（rbc）中PGK活性的概况。方法：68例PD患者和34例年龄匹配的非相关对照。通过建立的比色法测定红细胞的PGK活性，并用相同的红细胞样品进行标准化。结果：65岁及65岁以下PD组PGK活性显著高于对照组，而两组在任何年龄均无显著差异。在对照组中，PGK活性与衰老呈正相关，但在PD组中没有发现这一点。PD组多变量偏相关分析显示，PGK活性与纹状体多巴胺转运体闪烁特异结合率呈负相关。左旋多巴当量日剂量与酶活性无显著相关。结论：1)在相对年轻的PD患者和年龄正常的PD患者中可以检测到红细胞PGK活性升高；2)纹状体变性程度与PGK活性升高有关。当PGK检测被用作PD的诊断性生物标志物和治疗性监测PGK增强治疗时，这些都是重要的考虑因素。
Background: Impaired bioenergetics are partially involved in the pathogenesis of Parkinson's disease (PD). Phosphoglycerate kinase (PGK), an essential enzyme for glycolysis, has recently attracted attention due to its pathogenic role in PD and as a target for disease-modifying therapies. This study is aimed to evaluate the profiles of PGK activity in red blood cells (RBCs) of PD patients and controls. Methods: Sixty-eight PD patients and thirty-four age-matched unrelated controls were enrolled. PGK activities of RBCs were measured by the established colorimetric assay and standardized by the same RBC samples. Results: PGK activity of the PD group was significantly higher than that of the control group in participants aged sixty-five years or younger, whereas it was not significantly different between the two groups at any age. PGK activity was positively correlated with aging in the control group, but this was not noted in the PD group. On multivariable analysis by partial correlation in the PD group, PGK activity was negatively correlated with the specific binding ratio of dopamine transporter scintigraphy in the striatum. The levodopa-equivalent daily dose was not significantly correlated with the enzyme activity. Conclusion: The results support the following: 1) elevation of PGK activities in RBCs can be detected in relatively young PD patients and with normal aging; 2) the degree of striatonigral degeneration is associated with elevated PGK activities. These are important considerations when the PGK assay is applied as a diagnostic biomarker of PD and to therapeutically monitor PGK-enhancing treatments.