CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson's disease.
CNS dopamine oxidation and catechol-O-methyltransferase: importance in the etiology, pharmacotherapy, and dietary prevention of Parkinson's disease.
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中枢神经系统多巴胺氧化和儿茶酚-O-甲基转移酶：在帕金森病的病因学、药物治疗和饮食预防中的重要性。
DOI：
10.3892/ijmm.13.3.343
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发表时间：
2004
影响因子：
5.4
通讯作者：
B. Zhu
中科院分区：
文献类型：
--
作者：
B. Zhu
在这篇文章中，一个特别强调的概念发展和理解的独特的致病性变化，是土著的纹状体多巴胺能神经元作为一个重要的病因因素，在人类帕金森氏病（PD），以及对他们的临床意义的理解。具体来说，我已经讨论了帕金森病的中枢神经系统多巴胺氧化的病因作用，沿着的可用证据的批判性审查，以支持提出的假设。已知化学反应性多巴胺醌/半醌中间体具有高度神经毒性和潜在遗传毒性。有相当多的证据表明，长期使用左旋多巴加速PD的进展。相比之下，中枢作用的非儿茶酚多巴胺受体激动剂将是用于治疗PD（特别是晚期PD）的左旋多巴的极好替代品，因为这些药剂不会经历氧化还原循环而引起氧化性神经元损伤。儿茶酚-O-甲基转移酶（COMT）介导的儿茶酚胺类神经递质甲基化代谢是重要的一线解毒途径，其在帕金森病的病因和预防中的作用也进行了讨论。基于COMT介导的儿茶酚胺甲基化的调节，从机制上解释了高同型半胱氨酸血症是PD的致病因素，而维生素B6、B12和叶酸是保护因素。最后，根据本文所述的机制理解，提出了一种专门针对降低人类PD风险的新型饮食策略，包括食用营养均衡的饮食，其中含有足够（但不过量）的水果和蔬菜，沿着足够的S-腺苷-L-甲硫氨酸、维生素C、B6、B12和叶酸的饮食补充。据信，这些概念的发展也将有助于我们更好地了解其他与年龄有关的神经退行性疾病，如阿尔茨海默病和亨廷顿病。
In this article, a particular emphasis has been placed on the conceptual development and understanding of the unique pathogenic changes that are indigenous to the striatal dopaminergic neurons as an important etiological factor in human Parkinson's disease (PD) as well as on the understanding of their clinical implications. Specifically, I have discussed the etiological roles of central nervous system dopamine oxidation in PD, along with a critical review of the available evidence in support of the proposed hypotheses. The chemically-reactive dopamine quinone/semiquinone intermediates are known to be highly neurotoxic and potentially genotoxic. There is considerable evidence for the suggestion that the long-term use of levodopa accelerates the progression of PD. In comparison, centrally-acting non-catechol dopamine receptor agonists would be an excellent alternative to levodopa for the treatment of PD (particularly for late-stage PD) because these agents would not undergo redox cycling to cause oxidative neuronal damage. Catechol-O-methyltransferase (COMT)-mediated methylation metabolism of catecholamine neurotransmitters is a crucial first-line detoxification pathway, and its role in the causation and prevention of PD is also discussed. On the basis of the modulation of COMT-mediated methylation of catecholamines, it is mechanistically explained that hyperhomocysteinemia would be a pathogenic factor in PD whereas vitamins B6, B12, and folate would be a protective factor. Lastly, according to the mechanistic understanding developed here, a novel dietary strategy is proposed that is specifically tailored toward lowering the risk of human PD, which includes eating a nutritionally-balanced diet that contains adequate (but not excessive) amounts of fruits and vegetables, along with adequate dietary supplementation of S-adenosyl-L-methionine, vitamins C, B6, B12, and folate. It is believed that these conceptual developments would also aid in our better understanding of other age-related neurodegenerative disorders, such as Alzheimer's and Huntington's diseases.