Sun Yingying, Pham A Ninh, Hare Dominic J, Waite T David
Water Research Centre, School of Civil and Environmental Engineering, The University of New South Wales, Sydney, NSW, Australia.
Atomic Pathology Laboratory, Melbourne Dementia Research Centre at the Florey Institute of Neuroscience and Mental Health and The University of Melbourne, Parkville, VIC, Australia.
Front Neurosci. 2018 Nov 26;12:859. doi: 10.3389/fnins.2018.00859. eCollection 2018.
Parkinson's disease is the second most common neurodegenerative disease. While age is the most significant risk factor, the exact cause of this disease and the most effective approaches to mitigation remain unclear. It has long been proposed that dopamine may play a role in the pathology of Parkinson's disease in view of its ability to generate both protein-modifying quinones such as aminochrome and reactive oxygen species, especially in the presence of pathological iron accumulation in the primary site of neuron loss. Given the clinically measured acidosis of Parkinson's disease brain tissue, the interaction between dopamine and iron was investigated over a pH range of 7.4 to 6.5 with emphasis on the accumulation of toxic quinones and generation of reactive oxygen species. Our results show that the presence of iron accelerates the formation of aminochrome with ferrous iron (Fe[II]) being more efficient in this regard than ferric iron (Fe[III]). Our results further suggest that a reduced aminochrome rearrangement rate coupled with an enhanced turnover rate of Fe[II] as a result of brain tissue acidosis could result in aminochrome accumulation within cells. Additionally, under these conditions, the enhanced redox cycling of iron in the presence of dopamine aggravates oxidative stress as a result of the production of damaging reactive species, including hydroxyl radicals.
帕金森病是第二常见的神经退行性疾病。虽然年龄是最重要的风险因素，但这种疾病的确切病因以及最有效的缓解方法仍不清楚。长期以来，鉴于多巴胺能够产生蛋白质修饰醌类物质（如氨基色素）和活性氧，特别是在神经元损失的主要部位存在病理性铁积累的情况下，人们一直认为多巴胺可能在帕金森病的病理过程中发挥作用。鉴于帕金森病脑组织临床测量到的酸中毒情况，研究了多巴胺与铁在pH值7.4至6.5范围内的相互作用，重点关注有毒醌类物质的积累和活性氧的产生。我们的结果表明，铁的存在加速了氨基色素的形成，其中亚铁离子（Fe[II]）在这方面比铁离子（Fe[III]）更有效。我们的结果进一步表明，由于脑组织酸中毒导致氨基色素重排速率降低以及Fe[II]周转率提高，可能导致氨基色素在细胞内积累。此外，在这些条件下，多巴胺存在时铁的氧化还原循环增强，由于产生包括羟基自由基在内的有害活性物质，加剧了氧化应激。
