ABC efflux transporters at blood-central nervous system barriers and their implications for treating spinal cord disorders

作     者：Liam M. Koehn Liam M. Koehn

作者机构：Department of Pharmacology and Therapeutics the University of Melbourne 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第7期

页      面：1235-1242页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

主　　题：ABC transporters ATP-binding cassette BCRP blood-brain barrier blood-spinal cord barrier efflux MRP P-glycoprotein PGP spinal cord injury 

摘      要：The barriers present in the interfaces between the blood and the central nervous system form a major hurdle for the pharmacological treatment of central nervous system injuries and diseases.The family of ATP-binding cassette(ABC)transporters has been widely studied regarding efflux of medications at blood-central nervous system barriers.These efflux transporters include P-glycoprotein(abcb1),‘breast cancer resistance protein (abcg2)and the various‘multidrug resistance-associated proteins (abccs).Understanding which efflux transporters are present at the blood-spinal cord,blood-cerebrospinal fluid and cerebrospinal fluid-spinal cord barriers is necessary to determine their involvement in limiting drug transfer from blood to the spinal cord tissue.Recent developments in the blood-brain barrier field have shown that barrier systems are dynamic and the profile of barrier defenses can alter due to conditions such as age,disease and environmental challenge.This means that a true understanding of ABC efflux transporter expression and localization should not be one static value but instead a range that represents the complex patient subpopulations that exist.In the present review,the blood-central nervous system barrier literature is discussed with a focus on the impact of ABC efflux transporters on:(i)protecting the spinal cord from adverse effects of systemically directed drugs,and(ii)limiting centrally directed drugs from accessing their active sites within the spinal cord.