ABC transporters involved in respiratory and cholestatic diseases: From rare to very rare monogenic diseases.

Autor: Lakli M; Inserm, Université Paris-Saclay, Physiopathogenèse et traitement des maladies du foie, UMR_S 1193, Hepatinov, 91400 Orsay, France., Onnée M; Univ Paris Est Creteil, INSERM, IMRB, F-94010, Créteil, France., Carrez T; Université de Poitiers, Laboratoire Physiopathologie et Régulation des Transports Ioniques, Pôle Biologie Santé, 86000 Poitiers, France; ManRos Therapeutics, Hôtel de Recherche, Centre de Perharidy, 29680, Roscoff, France., Becq F; Université de Poitiers, Laboratoire Physiopathologie et Régulation des Transports Ioniques, Pôle Biologie Santé, 86000 Poitiers, France., Falguières T; Inserm, Université Paris-Saclay, Physiopathogenèse et traitement des maladies du foie, UMR_S 1193, Hepatinov, 91400 Orsay, France., Fanen P; Univ Paris Est Creteil, INSERM, IMRB, F-94010, Créteil, France; AP-HP, Département de Génétique Médicale, Hôpital Henri Mondor, F-94010, Créteil, France. Electronic address: pascale.fanen@inserm.fr.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Aug 05; Vol. 229, pp. 116468. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1016/j.bcp.2024.116468
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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