Erdő Franciska, Krajcsi Péter
Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary.
Solvo Biotechnology, A Charles River Company, Budapest, Hungary.
Front Aging Neurosci. 2019 Jul 30;11:196. doi: 10.3389/fnagi.2019.00196. eCollection 2019.
During the last decade, several articles have reported a relationship between advanced age and changes in the integrity of the blood-brain barrier (BBB). These changes were manifested not only in the morphology and structure of the cerebral microvessels but also in the expression and function of the transporter proteins in the luminal and basolateral surfaces of the capillary endothelial cells. Age-associated downregulation of the efflux pumps ATP-binding cassette transporters (ABC transporters) resulted in increased permeability and greater brain exposure to different xenobiotics and their possible toxicity. In age-related neurodegenerative pathologies like Alzheimer's disease (AD), the amyloid-β (Aβ) clearance decreased due to P-glycoprotein (P-gp) dysfunction, leading to higher brain exposure. In stroke, however, an enhanced P-gp function was reported in the cerebral capillaries, making it even more difficult to perform effective neuroprotective therapy in the infarcted brain area. This mini-review article focuses on the efflux functions of the transporters and receptors of the BBB in age-related brain pathologies and also in healthy aging.
在过去十年中，多篇文章报道了高龄与血脑屏障（BBB）完整性变化之间的关系。这些变化不仅体现在脑微血管的形态和结构上，还体现在毛细血管内皮细胞腔面和基底外侧表面转运蛋白的表达和功能上。与年龄相关的外排泵ATP结合盒转运蛋白（ABC转运蛋白）下调导致通透性增加，大脑对不同外源性物质及其潜在毒性的暴露增加。在阿尔茨海默病（AD）等与年龄相关的神经退行性疾病中，由于P-糖蛋白（P-gp）功能障碍，淀粉样β蛋白（Aβ）清除减少，导致大脑暴露增加。然而，在中风中，脑毛细血管中P-gp功能增强，使得在梗死脑区进行有效的神经保护治疗更加困难。这篇综述文章重点关注血脑屏障转运蛋白和受体在与年龄相关的脑部疾病以及健康衰老过程中的外排功能。
