Miyazaki Ikuko, Asanuma Masato
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Acta Med Okayama. 2008 Jun;62(3):141-50. doi: 10.18926/AMO/30942.
Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidationor auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicityin dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergicneuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopaminequinone-induced dysfunction of dopaminergic neurons.
氧化应激，包括在过量多巴胺的酶促氧化或自氧化过程中产生的活性氧或氮物种，被认为在多巴胺能神经毒性中起重要作用。多巴胺及其含有2个羟基残基的代谢产物在多巴胺能神经元细胞中发挥细胞毒性作用，主要是由于产生了高反应性的多巴胺和多巴醌。多巴胺和多巴醌可能通过在蛋白质上形成5-半胱氨酰儿茶酚而不可逆地改变蛋白质功能。此外，醌的形成与神经退行性疾病发病机制中的其他代表性假说密切相关，如线粒体功能障碍、炎症、氧化应激和泛素-蛋白酶体系统功能障碍。因此，多巴胺醌的致病作用最近集中在多巴胺能神经元特异性氧化应激上。在本文中，我们除了综述几种针对多巴胺醌诱导的多巴胺能神经元功能障碍的神经保护方法外，还主要回顾了最近关于醌形成致病性的研究。
