血脑屏障转运体：功能概述、阿尔茨海默病中的功能障碍以及治疗策略。

Blood-brain barrier transporters: An overview of function, dysfunction in Alzheimer's disease and strategies for treatment.

机构信息

Mental Health and Neuroscience Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, QUT, Brisbane, QLD, Australia.

Centre for Immunology and Infection Control, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia.

出版信息

Biochim Biophys Acta Mol Basis Dis. 2024 Feb;1870(2):166967. doi: 10.1016/j.bbadis.2023.166967. Epub 2023 Nov 24.

DOI:10.1016/j.bbadis.2023.166967

PMID:38008230

Abstract

The blood-brain-barrier (BBB) has a major function in maintaining brain homeostasis by regulating the entry of molecules from the blood to the brain. Key players in BBB function are BBB transporters which are highly expressed in brain endothelial cells (BECs) and critical in mediating the exchange of nutrients and waste products. BBB transporters can also influence drug delivery into the brain by inhibiting or facilitating the entry of brain targeting therapeutics for the treatment of brain disorders, such as Alzheimer's disease (AD). Recent studies have shown that AD is associated with a disrupted BBB and transporter dysfunction, although their roles in the development in AD are not fully understand. Modulation of BBB transporter activity may pose a novel approach to enhance the delivery of drugs to the brain for enhanced treatment of AD. In this review, we will give an overview of key functions of BBB transporters and known changes in AD. In addition, we will discuss current strategies for transporter modulation for enhanced drug delivery into the brain.

摘要

血脑屏障（BBB）通过调节血液中分子进入大脑的方式，对维持大脑内环境稳态起着重要作用。BBB 转运体是 BBB 功能的关键组成部分，在脑内皮细胞（BEC）中高度表达，对营养物质和废物的交换至关重要。BBB 转运体还可以通过抑制或促进靶向脑部治疗药物的进入，来影响药物向大脑的递送，从而治疗脑部疾病，如阿尔茨海默病（AD）。最近的研究表明，AD 与 BBB 破坏和转运体功能障碍有关，尽管它们在 AD 发展中的作用尚未完全阐明。调节 BBB 转运体的活性可能为增强药物向大脑的递送提供一种新的方法，从而增强 AD 的治疗效果。在这篇综述中，我们将概述 BBB 转运体的关键功能和 AD 中的已知变化。此外，我们将讨论目前用于增强药物向大脑递送的转运体调节策略。