Aquaporins in clinical medicine.
Aquaporins in clinical medicine.
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DOI：
10.1146/annurev-med-043010-193843
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发表时间：
2012
影响因子：
10.5
通讯作者：
Verkman AS
中科院分区：
文献类型：
--
作者：
Verkman AS
水通道蛋白是膜水通道的一个家族，其中一些也转运甘油。它们参与广泛的生理功能（包括水/盐稳态、外分泌液分泌和表皮水合作用）和人类疾病（包括青光眼、癌症、癫痫和肥胖）。在细胞水平，水通道蛋白介导的渗透性水跨细胞质膜转运促进跨上皮液体转运、细胞迁移和神经兴奋;水通道蛋白介导的甘油转运调节细胞增殖、脂肪细胞代谢和表皮水潴留。由水通道蛋白功能丧失突变引起的遗传疾病包括肾源性尿崩症和先天性白内障。视神经肌萎缩症的神经炎性脱髓鞘疾病以抗星形胶质细胞水通道水通道蛋白-4的致病性自身抗体为标志。水通道蛋白为基础的诊断和治疗的发展仍然有广阔的机会。疾病相关的水通道蛋白多态性开始被探索。在开发用于治疗某些类型的难治性水肿、脑肿胀、神经炎症、青光眼、癫痫、癌症、疼痛和肥胖症的小分子水通道蛋白调节剂方面有很大的前景。
The aquaporins are a family of membrane water channels, some of which also transport glycerol. They are involved in a wide range of physiological functions (including water/salt homeostasis, exocrine fluid secretion, and epidermal hydration) and human diseases (including glaucoma, cancer, epilepsy, and obesity). At the cellular level, aquaporin-mediated osmotic water transport across cell plasma membranes facilitates transepithelial fluid transport, cell migration, and neuroexcitation; aquaporin-mediated glycerol transport regulates cell proliferation, adipocyte metabolism, and epidermal water retention. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and congenital cataracts. The neuroinflammatory demyelinating disease neuromyelitis optica is marked by pathogenic autoantibodies against astrocyte water channel aquaporin-4. There remain broad opportunities for the development of aquaporin-based diagnostics and therapeutics. Disease-relevant aquaporin polymorphisms are beginning to be explored. There is great promise in the development of small-molecule aquaporin modulators for therapy of some types of refractory edema, brain swelling, neuroinflammation, glaucoma, epilepsy, cancer, pain, and obesity.