رسالة جامعية
Evaluation of the biodistribution and activity of new optimized readthrough molecules in Cystic fibrosis mouse model and other model systems
| العنوان: | Evaluation of the biodistribution and activity of new optimized readthrough molecules in Cystic fibrosis mouse model and other model systems |
|---|---|
| المؤلفون: | CORRAO, Federica |
| المساهمون: | LENTINI, Laura, PIGNATARO, Bruno Giuseppe |
| بيانات النشر: | Palermo Università degli Studi di Palermo |
| سنة النشر: | 2023 |
| المجموعة: | IRIS Università degli Studi di Palermo |
| مصطلحات موضوعية: | nonsense mutations, premature termination codon (PTC), translational readthrough-inducing drugs (TRIDS), Cystic fibrosis (CF), Lipopolysaccharides (LPS)-Responsive Beige-like Anchor (LRBA), Primary Immune Regulatory Disorders (PIRD), personalized medicine, in vitro and in vivo experimentation, Settore BIO/18 - Genetica |
| الوصف: | Nonsense mutations cause approximately 11% of inherited diseases, including Cystic fibrosis (CF), Duchenne Muscular Dystrophy (DMD), and some Primary Immune Regulatory Disorders (PIRD) can be mentioned. Nonsense mutations, also known as stop mutations, result in the presence of a premature termination codon (PTC) in the mRNA sequence, leading to premature translation termination. The consequence is the production of a truncated and non-functional protein, which is degraded. Simultaneously, the nonsense-mediated pathway (NMD) is activated, eliminating the available mRNA pool for translation. Currently, there is no cure for this genetic defect, resulting in life-threatening pathologies, such as CF or PIRD. CF is specifically caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. About 2500 different mutations are associated with CF with the most common being a three-base pair deletion causing the loss of phenylalanine at position 508 (ΔF508). Nonsense mutations in the CFTR gene represent approximately 10% of CF cases, resulting in the absence of functional protein and a more severe form of the disease. Apart from symptomatic approaches to care for CF patients, a pharmaceutical strategy targeting the specific genetic defect has been pursued. Heterocyclic scaffolds play a crucial role in the personalized medicinal approach, as demonstrated by numerous studies in the CF field. Similarly, PIRD is a heterogeneous group of immune diseases caused by 430 genes, among which Lipopolysaccharides (LPS)-Responsive Beige-like Anchor (LRBA) has been identified. The LRBA deficiency disease has been recently described, highlighting its multiple effects due to the ubiquitous localization of the LRBA protein, e.g., immune cells and endocytosis vesicles. Concerning nonsense mutations, in the last years, the experimental approach proposed for these genetic alterations is the premature termination codon (PTC) translational readthrough (TR) by small molecules. These molecules ... |
| نوع الوثيقة: | doctoral or postdoctoral thesis |
| اللغة: | English |
| العلاقة: | https://hdl.handle.net/10447/618889Test |
| الإتاحة: | https://hdl.handle.net/10447/618889Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.4DC34B9C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |