Aquaporins as targets for drug discovery.
Aquaporins as targets for drug discovery.
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DOI：
10.2174/138161207781368738
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发表时间：
2007-07
影响因子：
3.1
通讯作者：
A. Frigeri;G. P. Nicchia;M. Svelto
中科院分区：
文献类型：
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作者：
A. Frigeri;G. P. Nicchia;M. Svelto
细胞内的水分平衡是哺乳动物细胞的一个重要过程。水穿过细胞膜的运动是由渗透力和流体静力驱动的，并且该过程的速度取决于特定水通道蛋白水通道的存在。自从Peter Agre的研究小组对第一个水通道AQP1进行分子鉴定以来，在哺乳动物中已经发现了13个同源成员，它们具有不同程度的同源性。这些蛋白质在所有活细胞中的根本重要性是由它们在真核生物中从植物到哺乳动物的遗传保守性所暗示的。最近的一些研究已经揭示了哺乳动物水通道蛋白在生理学和病理生理学中的重要性，并且已经表明水通道蛋白表达和活性的药理学调节可以为治疗各种人类疾病提供新的工具，例如脑水肿、青光眼、肿瘤生长、充血性心力衰竭和肥胖，其中可能涉及水和小溶质转运。本文将重点介绍AQP在哺乳动物中的生理作用和病理参与，以及最近的一些治疗方法，如RNAi和免疫治疗，对AQP相关疾病的潜在用途。此外，战略，可以开发选择性水通道蛋白药物的发现将被介绍和讨论。
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.