Saito Yoshiro
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, 1-3 Miyakodani, Tatara, Kyotanabe, Kyoto, 610-0394, Japan.
Adv Exp Med Biol. 2017;1037:149-171. doi: 10.1007/978-981-10-6583-5_10.
Parkinson's disease is a progressive, age-related, neurodegenerative disorder, and oxidative stress is an important mediator in its pathogenesis. DJ-1 has been identified as a causative gene of a familial form of Parkinson's disease, PARK7, and plays a significant role in antioxidative defense, protecting cells from oxidative stress. A cysteine residue of DJ-1 at position 106 (Cys-106) is preferentially oxidized under oxidative stress. This reactive Cys-106 plays a critical role in the biological function of DJ-1, which could act as a sensor of oxidative stress by regulating antioxidative defense depending on Cys-106 oxidation. Thus, the levels of Cys-106-oxidized DJ-1 (oxDJ-1) could be a possible biomarker of oxidative stress. This chapter focuses on the properties of DJ-1 and oxDJ-1 levels as a biomarker of Parkinson's disease. In particular, the usability of these biomarkers to prevent and treat this neurodegenerative disease is discussed. Further, this section deals with the importance of identifying a biomarker of early-phase Parkinson's disease. Finally, this chapter summarizes the features of oxDJ-1 levels in the brain and blood as a biomarker candidate for early-phase Parkinson's disease based on our results using oxDJ-1-specific antibodies.
帕金森病是一种与年龄相关的进行性神经退行性疾病，氧化应激是其发病机制中的重要介质。DJ-1已被确定为家族性帕金森病PARK7的致病基因，在抗氧化防御中发挥重要作用，保护细胞免受氧化应激。DJ-1第106位的半胱氨酸残基（Cys-106）在氧化应激下优先被氧化。这种反应性的Cys-106在DJ-1的生物学功能中起关键作用，它可以通过根据Cys-106的氧化调节抗氧化防御来充当氧化应激的传感器。因此，Cys-106氧化的DJ-1（oxDJ-1）水平可能是氧化应激的一个生物标志物。本章重点介绍DJ-1的特性以及oxDJ-1水平作为帕金森病生物标志物的情况。特别讨论了这些生物标志物在预防和治疗这种神经退行性疾病方面的可用性。此外，本节还论述了识别早期帕金森病生物标志物的重要性。最后，本章根据我们使用oxDJ-1特异性抗体的结果，总结了大脑和血液中oxDJ-1水平作为早期帕金森病生物标志物候选物的特征。
