Drugging aquaporins

Abstract

Water is essential for all life because it is required for the proper functioning of the cells and tissues of all organisms. It crosses biological membranes down osmotic gradients through the pores of aquaporin membrane channels at rates of up to 3 billion molecules per second. In the twenty years since Peter Agre was awarded the 2003 Nobel Prize in Chemistry for the discovery of the aquaporin family, aquaporin structure and function have become established in the literature. As a consequence, we understand in fine detail the mechanism by which aquaporins facilitate membrane water flow while excluding protons. We also know that some aquaporins facilitate the permeation of other small neutral solutes, ions or even unexpected substrates across biological membranes. The thirteen aquaporins in the human body have been implicated in pathologies including oedema, epilepsy, cancer cell migration, tumour angiogenesis, metabolic disorders and inflammation. Surprisingly, however, there is no aquaporin-targeted drug in the clinic. Some scientists have therefore concluded that aquaporins are intrinsically non-druggable targets. Discovering medicines to treat disorders of water homeostasis is thus an enduring challenge for the aquaporin field. Success in this endeavour will meet the urgent clinical need of millions of patients suffering from a range of life-threatening conditions and for whom no pharmacological interventions are currently available.

Publication DOI: https://doi.org/10.1016/j.bbamem.2023.184164
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences
Aston University (General)
Funding Information: financial support was provided by the Biotechnology and Biological Sciences Research Council (BB/T00746X/1 and BB/P025927/1) and Horizon Europe (Grant agreement 847419). RMB reports a relationship with Estuar Pharmaceuticals that includes equity or stocks
Additional Information: © 2023 The Author. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: Aquaporin water channels,Membrane proteins,Inhibitors,Health,Disease
Publication ISSN: 1879-2642
Last Modified: 02 Dec 2024 08:53
Date Deposited: 22 Jan 2024 09:40
Full Text Link:
Related URLs: https://www.sci ... 0469?via%3Dihub (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2024-02
Published Online Date: 2023-05-03
Accepted Date: 2023-04-27
Authors: Bill, Roslyn (ORCID Profile 0000-0003-1331-0852)

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