囊性纤维化治疗的潜在新途径

Title:Novel Approaches for Potential Therapy of Cystic Fibrosis

Volume: 16 Issue: 9

Author(s): Victoria Sawczak, Paulina Getsy, Aliya Zaidi, Fei Sun, Khalequz Zaman and Benjamin Gaston

Affiliation:

关键词: 囊性纤维化跨膜电导调节因子(CFTR)，囊性纤维化，分子治疗，S-亚硝基硫醇，S-亚硝基化

摘要: Cystic fibrosis (CF) is a lethal autosomal recessive disease that causes severe damage to the respiratory and digestive systems. It results from a dysfunctional CF Transmembrane Conductance Regulator (CFTR) protein, which is a cAMP- regulated epithelial chloride channel. CFTR is also a subtype of the ABC-transporter superfamily, and is expressed primarily in the apical membrane of epithelial cells in the airways, pancreas, and intestines. A single amino acid deletion of phenylalanine (Phe) is the most common mutation in CF patients known as F508del-CFTR. Normally, wild-type CFTR is largely degraded before reaching the cell membrane and F508del-CFTR virtually never reaches the cell surface. Ultimately, our goal is to correct dysfunctional CFTR proteins in CF patients. Via high-throughput screening techniques, several novel compounds for potential drugs effective in reversing the molecular CF defect and prohibiting further progression of CF have recently been discovered. S-nitrosothiols (SNOs) are small, naturally occurring endogenous cell signaling compounds, which have potential relevance to human lung diseases, including CF. Remarkably, researchers have found that the level of SNOs are reduced in the CF airway. It was previously reported that different types of SNOs, such as GSNO and S-nitrosoglutathione diethyl ester will increase CFTR maturation and function at the plasma membrane in human airway epithelial cells. The mechanisms by which SNOs improve CFTR maturation remain elusive. Currently, clinical trials are still investigating the effectiveness and safety of novel corrector and potentiator drugs for F508del- CFTR. This review article offers a summary of our knowledge on the most up-to-date CF therapies.

Cite this article as:

Victoria Sawczak, Paulina Getsy, Aliya Zaidi, Fei Sun, Khalequz Zaman and Benjamin Gaston , Novel Approaches for Potential Therapy of Cystic Fibrosis, Current Drug Targets 2015; 16 (9) . https://dx.doi.org/10.2174/1389450116666150102113314