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Neuroinflammation in Friedreich’s Ataxia
Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron−sulphur clusters, and leading to progressive nervous system damage. Although the overt manifestations of FRDA i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181348/ https://www.ncbi.nlm.nih.gov/pubmed/35682973 http://dx.doi.org/10.3390/ijms23116297 |
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author | Apolloni, Savina Milani, Martina D’Ambrosi, Nadia |
author_facet | Apolloni, Savina Milani, Martina D’Ambrosi, Nadia |
author_sort | Apolloni, Savina |
collection | PubMed |
description | Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron−sulphur clusters, and leading to progressive nervous system damage. Although the overt manifestations of FRDA in the nervous system are mainly observed in the neurons, alterations in non-neuronal cells may also contribute to the pathogenesis of the disease, as recently suggested for other neurodegenerative disorders. In FRDA, the involvement of glial cells can be ascribed to direct effects caused by frataxin loss, eliciting different aberrant mechanisms. Iron accumulation, mitochondria dysfunction, and reactive species overproduction, mechanisms identified as etiopathogenic in neurons in FRDA, can similarly affect glial cells, leading them to assume phenotypes that can concur to and exacerbate neuron loss. Recent findings obtained in FRDA patients and cellular and animal models of the disease have suggested that neuroinflammation can accompany and contribute to the neuropathology. In this review article, we discuss evidence about the involvement of neuroinflammatory-related mechanisms in models of FRDA and provide clues for the modulation of glial-related mechanisms as a possible strategy to improve disease features. |
format | Online Article Text |
id | pubmed-9181348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91813482022-06-10 Neuroinflammation in Friedreich’s Ataxia Apolloni, Savina Milani, Martina D’Ambrosi, Nadia Int J Mol Sci Review Friedreich’s ataxia (FRDA) is a rare genetic disorder caused by mutations in the gene frataxin, encoding for a mitochondrial protein involved in iron handling and in the biogenesis of iron−sulphur clusters, and leading to progressive nervous system damage. Although the overt manifestations of FRDA in the nervous system are mainly observed in the neurons, alterations in non-neuronal cells may also contribute to the pathogenesis of the disease, as recently suggested for other neurodegenerative disorders. In FRDA, the involvement of glial cells can be ascribed to direct effects caused by frataxin loss, eliciting different aberrant mechanisms. Iron accumulation, mitochondria dysfunction, and reactive species overproduction, mechanisms identified as etiopathogenic in neurons in FRDA, can similarly affect glial cells, leading them to assume phenotypes that can concur to and exacerbate neuron loss. Recent findings obtained in FRDA patients and cellular and animal models of the disease have suggested that neuroinflammation can accompany and contribute to the neuropathology. In this review article, we discuss evidence about the involvement of neuroinflammatory-related mechanisms in models of FRDA and provide clues for the modulation of glial-related mechanisms as a possible strategy to improve disease features. MDPI 2022-06-04 /pmc/articles/PMC9181348/ /pubmed/35682973 http://dx.doi.org/10.3390/ijms23116297 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Apolloni, Savina Milani, Martina D’Ambrosi, Nadia Neuroinflammation in Friedreich’s Ataxia |
title | Neuroinflammation in Friedreich’s Ataxia |
title_full | Neuroinflammation in Friedreich’s Ataxia |
title_fullStr | Neuroinflammation in Friedreich’s Ataxia |
title_full_unstemmed | Neuroinflammation in Friedreich’s Ataxia |
title_short | Neuroinflammation in Friedreich’s Ataxia |
title_sort | neuroinflammation in friedreich’s ataxia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181348/ https://www.ncbi.nlm.nih.gov/pubmed/35682973 http://dx.doi.org/10.3390/ijms23116297 |
work_keys_str_mv | AT apollonisavina neuroinflammationinfriedreichsataxia AT milanimartina neuroinflammationinfriedreichsataxia AT dambrosinadia neuroinflammationinfriedreichsataxia |