血脑屏障上ABC转运体与中枢神经系统疾病相关性的研究进展

ABC转运体作为血脑屏障上一类重要的外排转运体,介导了内源性物质、药物及环境毒素的外排过程。疾病状态下,ABC转运体的功能及表达会发生改变,有些疾病会导致转运体过表达或者活性增强,引发耐药现象;还有一些疾病会引起转运体损伤,导致毒素蓄积脑内,加剧疾病的发展。将各种脑部疾病与ABC转运体之间的关系研究清楚,将有助于阐明致病机制,并可为改善脑部耐药及治疗中枢神经疾病提供思路和策略。本文就这一问题,综述了血脑屏障ABC转运体在多种疾病状态下功能与表达的变化,及这些改变对疾病产生的影响,并初步探讨了相关机制,提出了一些改善耐药和治疗疾病的策略。

Relationship between ABC transporters on the blood-brain barrier and central nervous diseases

ATP-binding cassette(ABC) transporters are an important type of transporters on the blood-brain barrier,which mediate the efflux of numerous endogenous substances,drugs and neurotoxicants from the brain parenchyma.Various diseases can change the expression and activity of ABC transporters.Up-regulation of ABC transporter expression and activity is a major factor to cause drug resistance in centre nervous system(CNS),while reduction of transporter expression and activity increases the accumulation of neurotoxicants in brain to aggravate the disease.Thus,elucidating the relationship between transporters and CNS diseases is critical for discovering pathogenic mechanism and providing the strategies for improving the therapeutic effects of CNS drugs.This review covers the alterations of ABC transporter expression and activity in CNS diseases,the effects of these changes on CNS diseases and the related signaling mechanisms.Finally,we also propose some strategies for improving neuroprotection and enhancing therapeutic drug delivery to the brain.