Original Research ARTICLE
Kinetic modelling of pH-dependent oxidation of dopamine by iron and its relevance to Parkinson’s disease
- 1University of New South Wales, Australia
- 2Florey Institute of Neuroscience and Mental Health, Australia
Parkinson’s disease is the second most common progressive neurodegenerative disease though 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 iron. 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.
Keywords: pH, Iron, Dopamine, aminochrome, Parkinsion's disease, Oxidative Stress
Received: 02 Aug 2018;
Accepted: 02 Nov 2018.
Edited by:Isabella Zanella, Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, Italy
Reviewed by:Luigi Bubacco, Università degli Studi di Padova, Italy
Ana Virel, Umeå University, Sweden
Copyright: © 2018 Waite, Sun, Pham and Hare. 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.
* Correspondence: Prof. David Waite, University of New South Wales, Sydney, Australia, email@example.com