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Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review)
An estimated one-third of genetic disorders are the result of mutations that generate premature termination codons (PTCs) within protein coding genes. These disorders are phenotypically diverse and consist of diseases that affect both young and old individuals. Various small molecules have been iden...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094583/ https://www.ncbi.nlm.nih.gov/pubmed/24939317 http://dx.doi.org/10.3892/ijmm.2014.1809 |
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author | KARIJOLICH, JOHN YU, YI-TAO |
author_facet | KARIJOLICH, JOHN YU, YI-TAO |
author_sort | KARIJOLICH, JOHN |
collection | PubMed |
description | An estimated one-third of genetic disorders are the result of mutations that generate premature termination codons (PTCs) within protein coding genes. These disorders are phenotypically diverse and consist of diseases that affect both young and old individuals. Various small molecules have been identified that are capable of modulating the efficiency of translation termination, including select antibiotics of the aminoglycoside family and multiple novel synthetic molecules, including PTC124. Several of these agents have proved their effectiveness at promoting nonsense suppression in preclinical animal models, as well as in clinical trials. In addition, it has recently been shown that box H/ACA RNA-guided peudouridylation, when directed to modify PTCs, can also promote nonsense suppression. In this review, we summarize our current understanding of eukaryotic translation termination and discuss various methods for promoting the read-through of disease-causing PTCs, as well as the current obstacles that stand in the way of using the discussed agents broadly in clinical practice. |
format | Online Article Text |
id | pubmed-4094583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-40945832014-07-14 Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) KARIJOLICH, JOHN YU, YI-TAO Int J Mol Med Articles An estimated one-third of genetic disorders are the result of mutations that generate premature termination codons (PTCs) within protein coding genes. These disorders are phenotypically diverse and consist of diseases that affect both young and old individuals. Various small molecules have been identified that are capable of modulating the efficiency of translation termination, including select antibiotics of the aminoglycoside family and multiple novel synthetic molecules, including PTC124. Several of these agents have proved their effectiveness at promoting nonsense suppression in preclinical animal models, as well as in clinical trials. In addition, it has recently been shown that box H/ACA RNA-guided peudouridylation, when directed to modify PTCs, can also promote nonsense suppression. In this review, we summarize our current understanding of eukaryotic translation termination and discuss various methods for promoting the read-through of disease-causing PTCs, as well as the current obstacles that stand in the way of using the discussed agents broadly in clinical practice. D.A. Spandidos 2014-08 2014-06-17 /pmc/articles/PMC4094583/ /pubmed/24939317 http://dx.doi.org/10.3892/ijmm.2014.1809 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Articles KARIJOLICH, JOHN YU, YI-TAO Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) |
title | Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) |
title_full | Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) |
title_fullStr | Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) |
title_full_unstemmed | Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) |
title_short | Therapeutic suppression of premature termination codons: Mechanisms and clinical considerations (Review) |
title_sort | therapeutic suppression of premature termination codons: mechanisms and clinical considerations (review) |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094583/ https://www.ncbi.nlm.nih.gov/pubmed/24939317 http://dx.doi.org/10.3892/ijmm.2014.1809 |
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