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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...

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Autores principales: Apolloni, Savina, Milani, Martina, D’Ambrosi, Nadia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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
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