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The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models
Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554808/ https://www.ncbi.nlm.nih.gov/pubmed/32937783 http://dx.doi.org/10.3390/ijms21186719 |
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author | Ohiomokhare, Samuel Olaolorun, Francis Ladagu, Amany Olopade, Funmilayo Howes, Melanie-Jayne R. Okello, Edward Olopade, James Chazot, Paul L. |
author_facet | Ohiomokhare, Samuel Olaolorun, Francis Ladagu, Amany Olopade, Funmilayo Howes, Melanie-Jayne R. Okello, Edward Olopade, James Chazot, Paul L. |
author_sort | Ohiomokhare, Samuel |
collection | PubMed |
description | Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK−1)(B9) Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK−1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD. |
format | Online Article Text |
id | pubmed-7554808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75548082020-10-14 The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models Ohiomokhare, Samuel Olaolorun, Francis Ladagu, Amany Olopade, Funmilayo Howes, Melanie-Jayne R. Okello, Edward Olopade, James Chazot, Paul L. Int J Mol Sci Article Parkinson’s disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain’s substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK−1)(B9) Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK−1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD. MDPI 2020-09-14 /pmc/articles/PMC7554808/ /pubmed/32937783 http://dx.doi.org/10.3390/ijms21186719 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ohiomokhare, Samuel Olaolorun, Francis Ladagu, Amany Olopade, Funmilayo Howes, Melanie-Jayne R. Okello, Edward Olopade, James Chazot, Paul L. The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models |
title | The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models |
title_full | The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models |
title_fullStr | The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models |
title_full_unstemmed | The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models |
title_short | The Pathopharmacological Interplay between Vanadium and Iron in Parkinson’s Disease Models |
title_sort | pathopharmacological interplay between vanadium and iron in parkinson’s disease models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554808/ https://www.ncbi.nlm.nih.gov/pubmed/32937783 http://dx.doi.org/10.3390/ijms21186719 |
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