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溶质载体(SLC)和 ABC 转运蛋白:血脑和血脑脊液屏障的表达、定位和种属差异。

SLC and ABC Transporters: Expression, Localization, and Species Differences at the Blood-Brain and the Blood-Cerebrospinal Fluid Barriers.

机构信息

Department of Pharmaceutical Sciences, University at Buffalo, State University of New York at Buffalo, Buffalo, New York, 14214-8033, USA.

Department of Pharmaceutics and Medicinal Chemistry, Thomas J Long School of Pharmacy and Health Sciences, University of the Pacific, 3601 Pacific Ave, Stockton, California, 95211, USA.

出版信息

AAPS J. 2017 Sep;19(5):1317-1331. doi: 10.1208/s12248-017-0110-8. Epub 2017 Jun 29.

Abstract

The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) separate the brain and cerebrospinal fluid (CSF) from the systemic circulation and represent a barrier to the uptake of both endogenous compounds and xenobiotics into the brain. For compounds whose passive diffusion is limited due to their ionization or hydrophilicity, membrane transporters can facilitate their uptake across the BBB or BCSFB. Members of the solute carrier (SLC) and ATP-binding case (ABC) families are present on these barriers. Differences exist in the localization and expression of transport proteins between the BBB and BCSFB, resulting in functional differences in transport properties. This review focuses on the expression, membrane localization, and different isoforms present at each barrier. Diseases that affect the central nervous system including brain tumors, HIV, Alzheimer's disease, Parkinson's disease, and stroke affect the integrity and expression of transporters at the BBB and BCSFB and will be briefly reviewed.

摘要

血脑屏障 (BBB) 和血脑脊液屏障 (BCSFB) 将大脑和脑脊液 (CSF) 与全身循环分隔开来,是阻止内源性化合物和外源性物质进入大脑的一道屏障。对于由于其电离或亲水性而导致被动扩散受限的化合物,膜转运体可以促进它们穿过 BBB 或 BCSFB 摄取。溶质载体 (SLC) 和 ATP 结合盒 (ABC) 家族的成员存在于这些屏障上。BBB 和 BCSFB 之间转运蛋白的定位和表达存在差异,导致转运特性的功能差异。本综述重点介绍了每个屏障上表达、膜定位和存在的不同同工型。影响中枢神经系统的疾病,包括脑肿瘤、HIV、阿尔茨海默病、帕金森病和中风,会影响 BBB 和 BCSFB 转运体的完整性和表达,本文将对此进行简要综述。

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