Recoding of Nonsense Mutation as a Pharmacological Strategy-Reference-Cited by-同舟云学术

Recoding of Nonsense Mutation as a Pharmacological Strategy

Published:2023-02-22 Issue:3 Volume:11 Page:659
ISSN:2227-9059
Container-title:Biomedicines
language:en
Short-container-title:Biomedicines

Author:

Temaj Gazmend¹^ORCID,Telkoparan-Akillilar Pelin²^ORCID,Nuhii Nexhibe³,Chichiarelli Silvia⁴^ORCID,Saha Sarmistha⁵^ORCID,Saso Luciano⁶⁷^ORCID

Affiliation:

1. Faculty of Pharmacy, College UBT, 10000 Prishtina, Kosovo

2. Department of Medical Biology, Faculty of Medicine, Yuksek Ihtisas University, 6530 Ankara, Turkey

3. Department of Pharmacy, Faculty of Medical Sciences, State University of Tetovo, 1200 Tetovo, North Macedonia

4. Department of Biochemical Sciences “A. Rossi-Fanelli”, Sapienza University of Rome, 00185 Rome, Italy

5. Department of Biotechnology, GLA University, Mathura 00185, Uttar Pradesh, India

6. Department of Cardiovascular, Endocrine-Metabolic Diseases, and Aging, Italian National Institute of Health, 00161 Rome, Italy

7. Department of Physiology and Pharmacology “Vittorio Erspamer”, Sapienza University of Rome, 00185 Rome, Italy

Abstract

Approximately 11% of genetic human diseases are caused by nonsense mutations that introduce a premature termination codon (PTC) into the coding sequence. The PTC results in the production of a potentially harmful shortened polypeptide and activation of a nonsense-mediated decay (NMD) pathway. The NMD pathway reduces the burden of unproductive protein synthesis by lowering the level of PTC mRNA. There is an endogenous rescue mechanism that produces a full-length protein from a PTC mRNA. Nonsense suppression therapies aim to increase readthrough, suppress NMD, or are a combination of both strategies. Therefore, treatment with translational readthrough-inducing drugs (TRIDs) and NMD inhibitors may increase the effectiveness of PTC suppression. Here we discuss the mechanism of PTC readthrough and the development of novel approaches to PTC suppression. We also discuss the toxicity and bioavailability of therapeutics used to stimulate PTC readthrough.

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Link

https://www.mdpi.com/2227-9059/11/3/659/pdf

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