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Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models
Protein synthesis is a fundamental process that underpins almost every aspect of cellular functioning. Intriguingly, despite their common function, recessive mutations in aminoacyl-tRNA synthetases (ARSs), the family of enzymes that pair tRNA molecules with amino acids prior to translation on the ri...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234152/ https://www.ncbi.nlm.nih.gov/pubmed/37274208 http://dx.doi.org/10.3389/fnins.2023.1182874 |
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author | Kalotay, Elizabeth Klugmann, Matthias Housley, Gary D. Fröhlich, Dominik |
author_facet | Kalotay, Elizabeth Klugmann, Matthias Housley, Gary D. Fröhlich, Dominik |
author_sort | Kalotay, Elizabeth |
collection | PubMed |
description | Protein synthesis is a fundamental process that underpins almost every aspect of cellular functioning. Intriguingly, despite their common function, recessive mutations in aminoacyl-tRNA synthetases (ARSs), the family of enzymes that pair tRNA molecules with amino acids prior to translation on the ribosome, cause a diverse range of multi-system disorders that affect specific groups of tissues. Neurological development is impaired in most ARS-associated disorders. In addition to central nervous system defects, diseases caused by recessive mutations in cytosolic ARSs commonly affect the liver and lungs. Patients with biallelic mutations in mitochondrial ARSs often present with encephalopathies, with variable involvement of peripheral systems. Many of these disorders cause severe disability, and as understanding of their pathogenesis is currently limited, there are no effective treatments available. To address this, accurate in vivo models for most of the recessive ARS diseases are urgently needed. Here, we discuss approaches that have been taken to model recessive ARS diseases in vivo, highlighting some of the challenges that have arisen in this process, as well as key results obtained from these models. Further development and refinement of animal models is essential to facilitate a better understanding of the pathophysiology underlying recessive ARS diseases, and ultimately to enable development and testing of effective therapies. |
format | Online Article Text |
id | pubmed-10234152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102341522023-06-02 Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models Kalotay, Elizabeth Klugmann, Matthias Housley, Gary D. Fröhlich, Dominik Front Neurosci Neuroscience Protein synthesis is a fundamental process that underpins almost every aspect of cellular functioning. Intriguingly, despite their common function, recessive mutations in aminoacyl-tRNA synthetases (ARSs), the family of enzymes that pair tRNA molecules with amino acids prior to translation on the ribosome, cause a diverse range of multi-system disorders that affect specific groups of tissues. Neurological development is impaired in most ARS-associated disorders. In addition to central nervous system defects, diseases caused by recessive mutations in cytosolic ARSs commonly affect the liver and lungs. Patients with biallelic mutations in mitochondrial ARSs often present with encephalopathies, with variable involvement of peripheral systems. Many of these disorders cause severe disability, and as understanding of their pathogenesis is currently limited, there are no effective treatments available. To address this, accurate in vivo models for most of the recessive ARS diseases are urgently needed. Here, we discuss approaches that have been taken to model recessive ARS diseases in vivo, highlighting some of the challenges that have arisen in this process, as well as key results obtained from these models. Further development and refinement of animal models is essential to facilitate a better understanding of the pathophysiology underlying recessive ARS diseases, and ultimately to enable development and testing of effective therapies. Frontiers Media S.A. 2023-05-09 /pmc/articles/PMC10234152/ /pubmed/37274208 http://dx.doi.org/10.3389/fnins.2023.1182874 Text en Copyright © 2023 Kalotay, Klugmann, Housley and Fröhlich. https://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 Kalotay, Elizabeth Klugmann, Matthias Housley, Gary D. Fröhlich, Dominik Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models |
title | Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models |
title_full | Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models |
title_fullStr | Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models |
title_full_unstemmed | Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models |
title_short | Recessive aminoacyl-tRNA synthetase disorders: lessons learned from in vivo disease models |
title_sort | recessive aminoacyl-trna synthetase disorders: lessons learned from in vivo disease models |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234152/ https://www.ncbi.nlm.nih.gov/pubmed/37274208 http://dx.doi.org/10.3389/fnins.2023.1182874 |
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