Aquaporins as Targets for Drug Discovery

Author(s): Antonio Frigeri, Grazia Paola Nicchia, Maria Svelto.

Journal Name: Current Pharmaceutical Design

Volume 13 , Issue 23 , 2007

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Abstract:

The intracellular hydric balance is an essential process of mammalian cells. The water movement across cell membranes is driven by osmotic and hydrostatic forces and the speed of this process is dependent on the presence of specific aquaporin water channels. Since the molecular identification of the first water channel, AQP1, by Peter Agres group, 13 homologous members have been found in mammals with varying degree of homology. The fundamental importance of these proteins in all living cells is suggested by their genetic conservation in eukaryotic organisms through plants to mammals. A number of recent studies have revealed the importance of mammalian AQPs in both physiology and pathophysiology and have suggested that pharmacological modulation of aquaporins expression and activity may provide new tools for the treatment of variety of human disorders, such as brain edema, glaucoma, tumour growth, congestive heart failure and obesity in which water and small solute transport may be involved. This review will highlight the physiological role and the pathological involvement of AQPs in mammals and the potential use of some recent therapeutic approaches, such as RNAi and immunotherapy, for AQP-related diseases. Furthermore, strategies that can be developed for the discovery of selective AQP-drugs will be introduced and discussed.

Keywords: Aquaporins, water channels, AQPs, drug discovery, inhibitors, tumous, brain edema

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Article Details

VOLUME: 13
ISSUE: 23
Year: 2007
Page: [2421 - 2427]
Pages: 7
DOI: 10.2174/138161207781368738
Price: $58

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