Abstract：
ATP-binding cassette (ABC) transporters constitute a 49-member superfamily in humans. These proteins, most of them being transmembrane, allow the active transport of an important variety of substrates across biological membranes, using ATP hydrolysis as an energy source. For an important proportion of these ABC transporters, genetic variations of the loci encoding them have been correlated with rare genetic diseases, including cystic fibrosis and interstitial lung disease (variations in CFTR/ABCC7 and ABCA3) as well as cholestatic liver diseases (variations in ABCB4 and ABCB11). In this review, we first describe these ABC transporters and how their molecular dysfunction may lead to human diseases. Then, we propose a classification of the genetic variants according to their molecular defect (expression, traffic, function and/or stability), which may be considered as a general guideline for all ABC transporters\' variants. Finally, we discuss recent progress in the field of targeted pharmacotherapy, which aim to correct specific molecular defects using small molecules. In conclusion, we are opening the path to treatment repurposing for diseases involving similar deficiencies in other ABC transporters.
摘要：
ATP结合盒(ABC)转运蛋白在人类中构成49个成员的超家族。这些蛋白质，它们大多数是跨膜的，允许各种重要的底物通过生物膜主动运输，使用ATP水解作为能源。对于这些ABC转运蛋白的重要比例，编码它们的基因座的遗传变异与罕见遗传疾病有关，包括囊性纤维化和间质性肺病（CFTR/ABCC7和ABCA3的变异）以及胆汁淤积性肝病（ABCB4和ABCB11的变异）。在这次审查中,我们首先描述这些ABC转运体及其分子功能障碍如何导致人类疾病。然后，我们提出了根据其分子缺陷对遗传变异进行分类(表达，交通,功能和/或稳定性)，这可以被认为是所有ABC转运蛋白变体的一般指南。最后,我们讨论了靶向药物治疗领域的最新进展，旨在使用小分子纠正特定的分子缺陷。总之,我们正在为涉及其他ABC转运蛋白中类似缺陷的疾病的治疗重新利用开辟道路.
