Aquaporins as targets for drug discovery.

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 Agre's 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.

journal_name

Curr Pharm Des

authors

Frigeri A,Nicchia GP,Svelto M

doi

10.2174/138161207781368738

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

2421-7

issue

23

eissn

1381-6128

issn

1873-4286

journal_volume

13

pub_type

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