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Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease
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 Par...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275323/ https://www.ncbi.nlm.nih.gov/pubmed/30534046 http://dx.doi.org/10.3389/fnins.2018.00859 |
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author | Sun, Yingying Pham, A. Ninh Hare, Dominic J. Waite, T. David |
author_facet | Sun, Yingying Pham, A. Ninh Hare, Dominic J. Waite, T. David |
author_sort | Sun, Yingying |
collection | PubMed |
description | 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 post-mortem 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. |
format | Online Article Text |
id | pubmed-6275323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62753232018-12-10 Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease Sun, Yingying Pham, A. Ninh Hare, Dominic J. Waite, T. David Front Neurosci Neuroscience 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 post-mortem 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. Frontiers Media S.A. 2018-11-26 /pmc/articles/PMC6275323/ /pubmed/30534046 http://dx.doi.org/10.3389/fnins.2018.00859 Text en Copyright © 2018 Sun, Pham, Hare and Waite. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Sun, Yingying Pham, A. Ninh Hare, Dominic J. Waite, T. David Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease |
title | Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease |
title_full | Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease |
title_fullStr | Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease |
title_full_unstemmed | Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease |
title_short | Kinetic Modeling of pH-Dependent Oxidation of Dopamine by Iron and Its Relevance to Parkinson's Disease |
title_sort | kinetic modeling of ph-dependent oxidation of dopamine by iron and its relevance to parkinson's disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275323/ https://www.ncbi.nlm.nih.gov/pubmed/30534046 http://dx.doi.org/10.3389/fnins.2018.00859 |
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