Aquaporins in Health and Disease New Molecular Targets for Drug Discovery

Since the discovery of Aquaporin-1 (AQP1) as a water channel, many studies have revealed the importance of aquaporins in mammalian physiology and pathophysiology as well as plant and microbial biology. The studies have also shown aquaporins as potential drug targets and targets for improving crop properties. Written by an international group of contributors at the forefront of the field, Aquaporins in Health and Disease: New Molecular Targets for Drug Discovery presents the latest research advances in aquaporins and other major intrinsic protein (MIP) channels. The first section of the book describes the general concepts of aquaporin channel function, genomic research, structure-function analysis of aquaporins and glycerol facilitators, and regulation by gating and trafficking, including yeast aquaporin regulation and function. The second section discusses the physiological and pathophysiological roles of aquaporins in humans and microbes. The final section covers the development of inhibitors of aquaporin function. The book’s epilogue offers future perspectives and directions, mainly in the area of aquaporin-based diagnostics and therapeutics. Stimulating future research on this important protein family, this book facilitates a paradigm shift in the understanding and roles of aquaporin membrane proteins in all biological settings. It encourages scientists to develop novel approaches for the treatment of human diseases based on aquaporin function or dysfunction.

Preface Søren Nielsen and Peter Agre MECHANISMS OF FLUID TRANSPORT IN CELLS AND EPITHELIAAquaporin Functional Detection: Basic Concepts on Water and Solute PermeationAna Madeira, Teresa F. Moura, and Graça SoveralAquaporin Discovery in the Genomic EraRafael Zardoya, Iker Irisarri, and Federico AbascalAquaporin Structure and SelectivityArdeschir Vahedi-Faridi and Andreas EngelRegulation of Eukaryotic AquaporinsMaria Nyblom and Susanna Törnroth-HorsefieldYeast Aquaporins and Aquaglyceroporins: A Matter of LifestyleMikael Andersson and Stefan Hohmann AQUAPORINS IN HEALTH AND DISEASEAquaporins in HealthAmaia Rodríguez, Leire Méndez-Giménez, and Gema FrühbeckRenal Aquaporins: Role in Water Balance DisordersTae-Hwan Kwon and Søren NielsenVasopressin and the Regulation of Aquaporin-2 in Health and DiseaseGiovanna Valenti and Grazia TammaHepatobiliary, Salivary Glands and Pancreatic Aquaporins in Health and DiseaseGiuseppe Calamita, Christine Delporte, and Raúl A. MarinelliAquaporins within the Central Nervous System: Implications for Oedema Following Traumatic CNS InjuryAnna V. Leonard and Renée J. TurnerAquaporins in Carcinogenesis: Water and Glycerol Channels as New Potential Drug TargetsChulso Moon and David MoonAttacking Aquaporin Water and Solute Channels of Human-Pathogenic Parasites: New Routes for Treatment?Julia von Bülow and Eric Beitz AQUAPORINS AS DRUG TARGETSAquaporins: Chemical Inhibition by Small MoleculesVincent J. Huber, Sören Wacker, and Michael RützlerDrug Discovery and Therapeutic Targets for Pharmacological Modulators of Aquaporin ChannelsJinxin V. Pei, Joshua L. Ameliorate, Mohamad Kourghi, Michael L. De Ieso, and Andrea J. YoolInorganic Compounds as Aquaporin Substrates or as Potent Inhibitors: A Coordination Chemistry Point of ViewAngela Casini and Andreia de Almeida EpilogueAngela Casini and Graça Soveral

Graça Soveral is an associate professor in the Pharmacy School at the University of Lisbon and principal investigator at the Research Institute for Medicines (iMed.ULisboa), where she coordinates the Biological Transport Unit. She received a PhD in pharmacy, sub-area biochemistry, from the University of Lisbon. Her main research area is membrane transport, with a special emphasis on water and solute transport in cell physiology and osmoregulation, aquaporin gating, and the discovery of aquaporin modulators for diagnostic and therapeutic applications. Søren Nielsen is a professor in the Department of Health Science and Technology at Aalborg University. He received an MD and a dr.med.sci degree in medical sciences from Aarhus University. His research involves the cell and molecular biological, physiological, and pathophysiological studies of aquaporin membrane water channels (aquaporins), sodium channels, and transporters in kidney and other organs to explore their role in water and sodium balance regulation in health and disease. Angela Casini is the chair of medicinal and bioinorganic chemistry in the School of Chemistry at Cardiff University. She received a PhD in chemistry from the University of Florence. Her work in medicinal and bioinorganic chemistry focuses on the study of the molecular mechanisms of anticancer metallodrugs and the development of metal compounds as chemical probes to detect protein functions. Peter Agre co-authored the preface of this book. He is a professor and director of the Johns Hopkins Malaria Research Institute at Johns Hopkins University. He received an MD from Johns Hopkins University Medical School. Dr. Agre was awarded the 2003 Nobel Prize in Chemistry for his pioneering studies on aquaporins.