Rust Ruslan, Sagare Abhay P, Zhang Mingzi, Zlokovic Berislav V, Kisler Kassandra
Department of Physiology and Neuroscience and the Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Expert Opin Drug Deliv. 2025 May;22(5):673-692. doi: 10.1080/17425247.2025.2480654. Epub 2025 Mar 21.
The blood-brain barrier (BBB) is a vascular endothelial membrane which restricts entry of toxins, cells, and microorganisms into the brain. At the same time, the BBB supplies the brain with nutrients, key substrates for DNA and RNA synthesis, and regulatory molecules, and removes metabolic waste products from brain to blood. BBB breakdown and/or dysfunction have been shown in neurogenerative disorders including Alzheimer's disease (AD). Current data suggests that these BBB changes may initiate and/or contribute to neuronal, synaptic, and cognitive dysfunction, and possibly other aspects of neurodegenerative processes.
We first briefly review recent studies uncovering molecular composition of brain microvasculature and examine the BBB as a possible therapeutic target in neurodegenerative disorders with a focus on AD. Current strategies aimed at protecting and/or restoring altered BBB functions are considered. The relevance of BBB-directed approaches to improve neuronal and synaptic function, and to slow progression of neurodegenerative processes are also discussed. Lastly, we review recent advancements in drug delivery across the BBB.
BBB breakdown and/or dysfunction can significantly affect neuronal and synaptic function and neurodegenerative processes. More attention should focus on therapeutics to preserve or restore BBB functions when considering treatments of neurodegenerative diseases and AD.
血脑屏障(BBB)是一种血管内皮膜,可限制毒素、细胞和微生物进入大脑。同时,血脑屏障为大脑提供营养物质、DNA和RNA合成的关键底物以及调节分子,并将代谢废物从大脑清除到血液中。血脑屏障的破坏和/或功能障碍已在包括阿尔茨海默病(AD)在内的神经退行性疾病中得到证实。目前的数据表明,这些血脑屏障的变化可能引发和/或导致神经元、突触和认知功能障碍,以及神经退行性过程的其他方面。
我们首先简要回顾最近揭示脑微血管分子组成的研究,并将血脑屏障作为神经退行性疾病(重点是AD)的一个可能治疗靶点进行研究。考虑了目前旨在保护和/或恢复改变的血脑屏障功能的策略。还讨论了针对血脑屏障的方法在改善神经元和突触功能以及减缓神经退行性过程进展方面的相关性。最后,我们回顾了跨血脑屏障药物递送的最新进展。
血脑屏障的破坏和/或功能障碍可显著影响神经元和突触功能以及神经退行性过程。在考虑神经退行性疾病和AD的治疗时,应更多关注保护或恢复血脑屏障功能的治疗方法。