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Nitric Oxide, Iron and Neurodegeneration

Iron is a crucial cofactor for several physiological functions in the brain including transport of oxygen, DNA synthesis, mitochondrial respiration, synthesis of myelin, and neurotransmitter metabolism. If iron concentration exceeds the capacity of cellular sequestration, excessive labile iron will...

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Autores principales: Liu, Chao, Liang, Mui Cheng, Soong, Tuck Wah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388708/
https://www.ncbi.nlm.nih.gov/pubmed/30833886
http://dx.doi.org/10.3389/fnins.2019.00114
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author Liu, Chao
Liang, Mui Cheng
Soong, Tuck Wah
author_facet Liu, Chao
Liang, Mui Cheng
Soong, Tuck Wah
author_sort Liu, Chao
collection PubMed
description Iron is a crucial cofactor for several physiological functions in the brain including transport of oxygen, DNA synthesis, mitochondrial respiration, synthesis of myelin, and neurotransmitter metabolism. If iron concentration exceeds the capacity of cellular sequestration, excessive labile iron will be harmful by generating oxidative stress that leads to cell death. In patients suffering from Parkinson disease, the total amount of iron in the substantia nigra was reported to increase with disease severity. High concentrations of iron were also found in the amyloid plaques and neurofibrillary tangles of human Alzheimer disease brains. Besides iron, nitric oxide (NO) produced in high concentration has been associated with neurodegeneration. NO is produced as a co-product when the enzyme NO synthase converts L-arginine to citrulline, and NO has a role to support normal physiological functions. When NO is produced in a high concentration under pathological conditions such as inflammation, aberrantly S-nitrosylated proteins can initiate neurodegeneration. Interestingly, NO is closely related with iron homeostasis. Firstly, it regulates iron-related gene expression through a system involving iron regulatory protein and its cognate iron responsive element (IRP-IRE). Secondly, it modified the function of iron-related protein directly via S-nitrosylation. In this review, we examine the recent advances about the potential role of dysregulated iron homeostasis in neurodegeneration, with an emphasis on AD and PD, and we discuss iron chelation as a potential therapy. This review also highlights the changes in iron homeostasis caused by NO. An understanding of these mechanisms will help us formulate strategies to reverse or ameliorate iron-related neurodegeneration in diseases such as AD and PD.
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spelling pubmed-63887082019-03-04 Nitric Oxide, Iron and Neurodegeneration Liu, Chao Liang, Mui Cheng Soong, Tuck Wah Front Neurosci Neuroscience Iron is a crucial cofactor for several physiological functions in the brain including transport of oxygen, DNA synthesis, mitochondrial respiration, synthesis of myelin, and neurotransmitter metabolism. If iron concentration exceeds the capacity of cellular sequestration, excessive labile iron will be harmful by generating oxidative stress that leads to cell death. In patients suffering from Parkinson disease, the total amount of iron in the substantia nigra was reported to increase with disease severity. High concentrations of iron were also found in the amyloid plaques and neurofibrillary tangles of human Alzheimer disease brains. Besides iron, nitric oxide (NO) produced in high concentration has been associated with neurodegeneration. NO is produced as a co-product when the enzyme NO synthase converts L-arginine to citrulline, and NO has a role to support normal physiological functions. When NO is produced in a high concentration under pathological conditions such as inflammation, aberrantly S-nitrosylated proteins can initiate neurodegeneration. Interestingly, NO is closely related with iron homeostasis. Firstly, it regulates iron-related gene expression through a system involving iron regulatory protein and its cognate iron responsive element (IRP-IRE). Secondly, it modified the function of iron-related protein directly via S-nitrosylation. In this review, we examine the recent advances about the potential role of dysregulated iron homeostasis in neurodegeneration, with an emphasis on AD and PD, and we discuss iron chelation as a potential therapy. This review also highlights the changes in iron homeostasis caused by NO. An understanding of these mechanisms will help us formulate strategies to reverse or ameliorate iron-related neurodegeneration in diseases such as AD and PD. Frontiers Media S.A. 2019-02-18 /pmc/articles/PMC6388708/ /pubmed/30833886 http://dx.doi.org/10.3389/fnins.2019.00114 Text en Copyright © 2019 Liu, Liang and Soong. 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
Liu, Chao
Liang, Mui Cheng
Soong, Tuck Wah
Nitric Oxide, Iron and Neurodegeneration
title Nitric Oxide, Iron and Neurodegeneration
title_full Nitric Oxide, Iron and Neurodegeneration
title_fullStr Nitric Oxide, Iron and Neurodegeneration
title_full_unstemmed Nitric Oxide, Iron and Neurodegeneration
title_short Nitric Oxide, Iron and Neurodegeneration
title_sort nitric oxide, iron and neurodegeneration
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388708/
https://www.ncbi.nlm.nih.gov/pubmed/30833886
http://dx.doi.org/10.3389/fnins.2019.00114
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