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Readthrough Activators and Nonsense-Mediated mRNA Decay Inhibitor Molecules: Real Potential in Many Genetic Diseases
Nesrine Benslimane1, Camille Loret1, Pauline Chazelas1,2
1GEIST Institute, University of Limoges, NeurIT UR 20218, F-87000 Limoges, France.
Pharmaceuticals (Basel, Switzerland)
|March 28, 2024
Summary
Small molecules can help bypass premature termination codons (PTCs) by promoting therapeutic readthrough. This approach shows promise for treating neuromuscular disorders, including peripheral neuropathies.
Area of Science:
- Molecular Biology
- Pharmacology
- Genetics
Background:
- Nonsense mutations create premature termination codons (PTCs), leading to mRNA degradation or truncated proteins.
- Therapeutic strategies are being developed to overcome the effects of PTCs.
Purpose of the Study:
- To review existing therapeutic strategies for bypassing premature termination codons (PTCs).
- To explore the potential of small-molecule drugs in promoting PTC readthrough for treating genetic disorders.
Main Methods:
- Review of pharmacological molecules and their mechanisms of action in promoting PTC readthrough.
- Analysis of studies testing readthrough molecules in various disease models.
Main Results:
- Small-molecule drugs can induce the readthrough of PTCs by facilitating near-cognate tRNA incorporation.
- Positive outcomes in neuromuscular disorder models suggest efficacy for peripheral neuropathies.
Conclusions:
- PTC readthrough using small molecules is a viable therapeutic strategy.
- This approach holds significant potential for treating peripheral neuropathies and other genetic disorders caused by nonsense mutations.
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