Ma Yilun, Dong Taiwei, Luan Fei, Yang Juanjuan, Miao Feng, Wei Peifeng
College of Pharmacy and First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, China.
National Drug Clinical Trial Agency, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central Hospital, Xi'an, Shaanxi Province, China.
Neural Regen Res. 2025 Aug 1;20(8):2133-2152. doi: 10.4103/NRR.NRR-D-24-00191. Epub 2024 Sep 6.
The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment; however, the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood. The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function. It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier, in addition to the transport of lipids, such as docosahexaenoic acid, across the blood-brain barrier. Furthermore, an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases; however, little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier. This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier, including their basic structures and functions, cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier, and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability. This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date. This will not only help to elucidate the pathogenesis of neurological diseases, improve the accuracy of laboratory diagnosis, and optimize clinical treatment strategies, but it may also play an important role in prognostic monitoring. In addition, the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized. This review may contribute to the development of new approaches for the treatment of neurological diseases.
血脑屏障的功能和结构完整性对于维持脑微环境的稳态至关重要;然而,血脑屏障形成和功能的分子机制仍知之甚少。已确定含有2A的主要易化子超家族结构域是血脑屏障功能的关键调节因子。它在促进和维持血脑屏障的形成及功能稳定性方面发挥着关键作用,此外还参与了二十二碳六烯酸等脂质跨血脑屏障的转运。此外,越来越多的研究表明,含有2A的主要易化子超家族结构域参与了多种神经系统疾病中血脑屏障功能障碍的分子机制;然而,关于含有2A的主要易化子超家族结构域影响血脑屏障的机制却知之甚少。本文对含有2A的主要易化子超家族结构域蛋白与血脑屏障之间的密切关系进行了全面系统的综述,包括它们的基本结构和功能、含有2A的主要易化子超家族结构域与血脑屏障之间的交联,以及对脂质转运和血脑屏障通透性调节的深入研究。这一全面系统的综述有助于深入了解含有2A的主要易化子超家族结构域蛋白在维持血脑屏障结构和功能方面的重要作用以及迄今为止的研究进展。这不仅有助于阐明神经系统疾病的发病机制、提高实验室诊断的准确性和优化临床治疗策略,还可能在预后监测中发挥重要作用。此外,总结了含有2A的主要易化子超家族结构域对各种疾病中血脑屏障渗漏的影响以及跨血脑屏障药物递送的研究进展。这篇综述可能有助于开发治疗神经系统疾病的新方法。