Recoding of Nonsense Mutation as a Pharmacological Strategy

Temaj G., Telkoparan-Akillilar P., Nuhii N., Chichiarelli S., Saha S., Saso L.

Biomedicines, cilt.11, sa.3, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 11 Sayı: 3
  • Basım Tarihi: 2023
  • Doi Numarası: 10.3390/biomedicines11030659
  • Dergi Adı: Biomedicines
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Directory of Open Access Journals
  • Anahtar Kelimeler: aminoglycoside, drug inhibition, non-aminoglycosides, nonsense-mediated decay, pharmacological perspective, pharmacological therapy, SURF complex
  • Gazi Üniversitesi Adresli: Hayır

Özet

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.