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Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that t...

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Autores principales: van Vuuren, Marthinus Janse, Nell, Theodore Albertus, Carr, Jonathan Ambrose, Kell, Douglas B., Pretorius, Etheresia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823713/
https://www.ncbi.nlm.nih.gov/pubmed/33383805
http://dx.doi.org/10.3390/biom11010030
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author van Vuuren, Marthinus Janse
Nell, Theodore Albertus
Carr, Jonathan Ambrose
Kell, Douglas B.
Pretorius, Etheresia
author_facet van Vuuren, Marthinus Janse
Nell, Theodore Albertus
Carr, Jonathan Ambrose
Kell, Douglas B.
Pretorius, Etheresia
author_sort van Vuuren, Marthinus Janse
collection PubMed
description Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby bacterial inflammagens may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation, pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.
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spelling pubmed-78237132021-01-24 Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease van Vuuren, Marthinus Janse Nell, Theodore Albertus Carr, Jonathan Ambrose Kell, Douglas B. Pretorius, Etheresia Biomolecules Review Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby bacterial inflammagens may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation, pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease. MDPI 2020-12-29 /pmc/articles/PMC7823713/ /pubmed/33383805 http://dx.doi.org/10.3390/biom11010030 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 Review
van Vuuren, Marthinus Janse
Nell, Theodore Albertus
Carr, Jonathan Ambrose
Kell, Douglas B.
Pretorius, Etheresia
Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease
title Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease
title_full Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease
title_fullStr Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease
title_full_unstemmed Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease
title_short Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease
title_sort iron dysregulation and inflammagens related to oral and gut health are central to the development of parkinson’s disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823713/
https://www.ncbi.nlm.nih.gov/pubmed/33383805
http://dx.doi.org/10.3390/biom11010030
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