水通道蛋白在中枢神经系统疾病中的药理调控前景

Natalia S. Ponamareva, Vasiliy E. Novikov, Elena V. Pozhilova
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引用次数: 0

摘要

本文对水通道蛋白在中枢神经系统疾病发病机制中的作用及其药理调控的可能性的科学研究结果进行了分析。水通道蛋白(AQP)是一种参与水和其他物质跨膜运输的蛋白质。它们形成细胞膜的水通道,广泛存在于各种哺乳动物细胞中,包括人脑和脊髓细胞的细胞膜。迄今为止,已经发现了大约300种水通道蛋白家族的蛋白质,其中13种(AQP0AQP12)已在人类细胞中被鉴定出来。不同类型AQP在中枢神经系统结构中的定位、它们的功能活性和参与中枢神经系统疾病的发展是不同的。在中枢神经系统中主要有AQP1、AQP4和AQP9三种类型的aqp。科学研究结果表明,AQP在维持中枢神经系统水盐稳态和保证中枢神经系统生理过程中发挥着重要作用,也证实了AQP在多种中枢神经系统疾病(各种原因的脑水肿、肿瘤细胞的侵袭和瘤周水肿的形成、自身免疫性疾病视髓炎、阿尔茨海默病的发展)的发病过程中所起的作用。水通道蛋白功能活性的药理调节可影响这些疾病的病程。因此,人们自然对能够改变AQP表达的药物感兴趣。 水通道蛋白家族的蛋白质提供水的跨膜运输,并在中枢神经系统病理状况的发展中发挥重要作用。它们可能是许多中枢神经系统疾病药理作用的潜在靶点。寻找和研究影响AQP表达和功能活性的药物在病理上是合理的,是开发脑水肿、恶性脑肿瘤等中枢神经系统疾病药物治疗策略的一个有希望的方向。
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Prospects of pharmacological regulation of aquaporin function in CNS diseases
The review analyzes the results of scientific research on the role of aquaporins in the pathogenesis of CNS diseases and the possibility of their pharmacological regulation. Aquaporins (AQP) are proteins involved in the transmembrane transport of water and other substances. They form the water channels of cell membranes and are widely represented in various mammalian cells, including the membranes of human brain and spinal cord cells. To date, about 300 types of proteins of the aquaporin family have been discovered, of which 13 (AQP0AQP12) have been identified in human cells. Localization of different types of AQP in CNS structures, their functional activity and involvement in the development of CNS diseases differ. There are mainly three types of AQPs in the central nervous system: AQP1, AQP4 and AQP9. The results of scientific research indicate the most important role of AQP in maintaining water-salt homeostasis and ensuring physiological processes in the central nervous system, and also confirm the role of AQP in the pathogenesis of a number of diseases of the central nervous system (cerebral edema of various genesis, invasion of tumor cells and the formation of peritumorous edema, in the development of autoimmune diseases opticomyelitis, Alzheimers disease). Pharmacological regulation of the functional activity of aquaporins can influence the course of these diseases. Therefore, there is a natural interest in drugs that can change the expression of AQP. Proteins of the aquaporin family provide transmembrane transport of water and play an essential role in the development of pathological conditions of the central nervous system. They can be potential targets for pharmacological effects in a number of diseases of the central nervous system. The search and study of drugs affecting the expression and functional activity of AQP is pathogenetically justified and is a promising direction in the development of pharmacotherapy strategies for cerebral edema, malignant brain tumors and other CNS diseases.
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