Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kalotay, Elizabeth, Klugmann, Matthias, Housley, Gary D., Fröhlich, Dominik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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
_version_ 1785052420553834496
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
work_keys_str_mv AT kalotayelizabeth recessiveaminoacyltrnasynthetasedisorderslessonslearnedfrominvivodiseasemodels
AT klugmannmatthias recessiveaminoacyltrnasynthetasedisorderslessonslearnedfrominvivodiseasemodels
AT housleygaryd recessiveaminoacyltrnasynthetasedisorderslessonslearnedfrominvivodiseasemodels
AT frohlichdominik recessiveaminoacyltrnasynthetasedisorderslessonslearnedfrominvivodiseasemodels