在囊性纤维化中ENaC作为一个可能的作用靶点

Title:Targeting ENaC as a Molecular Suspect in Cystic Fibrosis

Volume: 16 Issue: 9

Author(s): Nadine Bangel-Ruland, Katja Tomczak and Wolf-Michael Weber

Affiliation:

关键词: 阿米洛利，ASOs，囊性纤维化，囊性纤维化跨膜电导调节因子(CFTR)，ENaC，siRNA

摘要: Cystic fibrosis (CF) is the most common life shortening autosomal inherited disorder, affecting 1 in 2500 newborns in the Caucasian population. In CF the lung pathology is associated with dehydration of the airways epithelial surface which in part results from Na⁺ hyperabsorption via the epithelial sodium channel (ENaC). The molecular mechanisms of this Na⁺ hyperabsorption and its correlation with the underlying genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR) are not fully understood. However, it is obvious that a reduced Cl^- secretion by CFTR and an enhanced Na+ absorption through ENaC lead to the so far incurable disease. Therefore, it could be indicated to pursue a double-tracked strategy in that way enabling Cl^- secretion by a reconstitution of the defect CFTR as well as blocking ENaC to prevent Na⁺ hyperabsorption. Since the cloning of CFTR great efforts have been done in delivery of CFTR for the correction of the reduced Cl^- secretion. Positive benefits for the inhibition of the CF related Na⁺ hyperabsorption offer technologies using small molecule inhibitors like ASOs or siRNA, which target translation and knockdown of ENaC, respectively. In this review we discuss possible CFTR/ENaC interactions in the context of CF, describe ENaC structure as well as some of the numerous attempts that were performed to prevent the Na⁺ hyperabsorption in CF related lung disease. Thus, we give a short summary of e.g. amiloride therapy approaches and focus on inventive blocking efforts using ASOs and siRNA.

Cite this article as:

Nadine Bangel-Ruland, Katja Tomczak and Wolf-Michael Weber , Targeting ENaC as a Molecular Suspect in Cystic Fibrosis, Current Drug Targets 2015; 16 (9) . https://dx.doi.org/10.2174/1389450116666141212101626