Chang Kuo-Hsuan, Chen Chiung-Mei
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Antioxidants (Basel). 2020 Jul 8;9(7):597. doi: 10.3390/antiox9070597.
Parkinson's disease (PD) is caused by progressive neurodegeneration of dopaminergic (DAergic) neurons with abnormal accumulation of α-synuclein in substantia nigra (SN). Studies have suggested the potential involvement of dopamine, iron, calcium, mitochondria and neuroinflammation in contributing to overwhelmed oxidative stress and neurodegeneration in PD. Function studies on PD-causative mutations of , , , , , and further indicate the role of oxidative stress in the pathogenesis of PD. Therefore, it is reasonable that molecules involved in oxidative stress, such as DJ-1, coenzyme Q10, uric acid, 8-hydroxy-2'-deoxyguanosin, homocysteine, retinoic acid/carotenes, vitamin E, glutathione peroxidase, superoxide dismutase, xanthine oxidase and products of lipid peroxidation, could be candidate biomarkers for PD. Applications of antioxidants to modulate oxidative stress could be a strategy in treating PD. Although a number of antioxidants, such as creatine, vitamin E, coenzyme Q10, pioglitazone, melatonin and desferrioxamine, have been tested in clinical trials, none of them have demonstrated conclusive evidence to ameliorate the neurodegeneration in PD patients. Difficulties in clinical studies may be caused by the long-standing progression of neurodegeneration, lack of biomarkers for premotor stage of PD and inadequate drug delivery across blood-brain barrier. Solutions for these challenges will be warranted for future studies with novel antioxidative treatment in PD patients.
帕金森病（PD）是由黑质（SN）中多巴胺能（DAergic）神经元进行性神经变性以及α-突触核蛋白异常积聚所致。研究表明，多巴胺、铁、钙、线粒体和神经炎症可能参与导致PD中过度的氧化应激和神经变性。对PD致病突变 、 、 、 、 、 和 的功能研究进一步表明氧化应激在PD发病机制中的作用。因此，参与氧化应激的分子，如DJ-1、辅酶Q10、尿酸、8-羟基-2'-脱氧鸟苷、同型半胱氨酸、视黄酸/类胡萝卜素、维生素E、谷胱甘肽过氧化物酶、超氧化物歧化酶、黄嘌呤氧化酶和脂质过氧化产物，有可能成为PD的生物标志物。应用抗氧化剂来调节氧化应激可能是治疗PD的一种策略。尽管一些抗氧化剂，如肌酸、维生素E、辅酶Q10、吡格列酮、褪黑素和去铁胺，已在临床试验中进行了测试，但它们均未显示出确凿证据能改善PD患者的神经变性。临床研究中的困难可能是由神经变性的长期进展、缺乏PD运动前期的生物标志物以及血脑屏障药物递送不足所致。对于未来PD患者新型抗氧化治疗的研究，有必要解决这些挑战。
