Targeted Pharmacotherapies for Defective ABC Transporters
Abstract
Human ABC (ATP Binding Cassette) transporters form a superfamily of forty-eight transmembrane proteins, which transport their substrates across biological membranes against important concentration gradients, in an energy-dependent manner. Gene variations in approximately half of these transporters have been identified in subjects with rare and often severe genetic diseases, highlighting the importance of their biological function. For missense variations leading to defects in ABC transporters, the current challenge is to identify new molecules with therapeutic potential able to rescue the induced molecular deficiency. In this review, we first address the progress provided by emerging pharmacotherapies in cystic fibrosis, the most frequent monogenic disease caused by variations of an ABC transporter, i.e. ABCC7/CFTR. Then, we enlarge the topic to the other ABC transporters, more notably to canalicular ABC transporters, the variations of which cause rare hepatobiliary diseases, and we discuss the first promising attempts aiming to correct molecular defects of these proteins.
Origin : Files produced by the author(s)
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