摘要
水通道蛋白(aquaporin,AQP)是一组特异通透水和某些特定小分子的细胞膜通道蛋白。水通道蛋白4(aquaporin 4,AQP4)在大脑组织中表达丰富,脑星形胶质细胞、视网膜Müller细胞、内耳支持细胞、嗅觉上皮支持细胞中均有AQP4表达。AQP4具有两个蛋白亚型:M1和M23。M23在细胞膜能够形成正交排列结构。研究结果表明AQP4在脑组织中介导水的转运并可能在中枢神经系统生理功能中起重要作用。癫痫的发病过程中AQP4表达上调,AQP4促进细胞毒性脑水肿的发生,在血管源性脑水肿中辅助清除多余脑积水,并且AQP4参与视神经脊髓炎的发生。本文综述了AQP4在中枢神经系统的生理功能和在中枢神经系统疾病,包括癫痫、脑水肿、视神经脊髓炎等发病机制以及治疗方面的作用。
The aquaporins(AQP)are a family of water-transporting proteins. Aquaporin4 (AQP4)is expressed in astrocytes throughout the central nervous system,as well as in Müller cells in the retina,Claudius/Hensen cells in the inner ear and olfactory epithelial cells. There are two AQP4 isoforms,M1 and M23,produced by alternative splicing. M23 AQP4 forms heterotetramers that assemble in the cell membrane in supramolecular structures called orthogonal arrays of particles(OAP). Phenotype analysis of AQP4-null mice indicates the involvement of AQP4 in brain and spinal cord water balance,astrocyte migration, neural signal transduction and neuroinflammation. AQP4-null mice manifest reduced brain swelling in cytotoxic cerebral edema,but increased brain swelling in vasogenic edema and hydrocephalus. AQP4 deficiency increases seizure duration. AQP4 is also involved in the neuroinflammatory demyelinating disease neuromyelitis optica,where autoantibodies(NMO-IgG)targeting AQP4 produce astrocyte damage and inflammation. This review summarizes the effect and possible mechanism of AQP4 in nervous system diseases,such as epilepsy,edema and neuromyelitis optica.
出处
《神经药理学报》
2012年第1期20-27,共8页
Acta Neuropharmacologica
基金
国家重大新药创制科技专项(No.2009ZX09103)
国家自然科学基金资助项目(No.30870921
81170632
81261160507)
科技部国际科技合作与交流专项(No.2012DFA11070)
教育部博士点基金资助项目(No.20100001110047)
关键词
水通道蛋白4
正交排列结构
癫痫
脑水肿
视神经脊髓炎
aquaporin4(AQP4)
orthogonal arrays of particle
epilepsy
brain edema
neuromyelitis optica
