Nasrollahi Ava, Yao Yao
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Matrix Biol. 2025 May;137:33-41. doi: 10.1016/j.matbio.2025.02.005. Epub 2025 Mar 1.
The blood-brain barrier (BBB) is a dynamic structure that maintains brain homeostasis. BBB breakdown is a key pathological hallmark of almost all neurological diseases. Although the regulation of BBB integrity by different cells has been extensively studied, the function of its non-cellular component-the basal lamina in BBB regulation remains largely unknown. Laminin, a trimeric protein with multiple isoforms, is one of the most important constituents of the basal lamina. In the CNS, different cells synthesize distinct laminin isoforms, which differentially regulate BBB integrity in both physiological and pathological conditions. A thorough understanding of laminin expression and function in BBB integrity could lead to the identification of novel therapeutic targets and potentially result in effective treatments for neurological disorders involving BBB disruption. Here in this review, we first briefly introduce the BBB and basal lamina with a focus on laminin. Next, we elucidate laminin expression and its function in BBB maintenance/repair in a cell-specific manner. Potential functional compensation among laminin isoforms is also discussed. Last, current challenges in the field and future directions are summarized. Our goal is to provide a synthetic review to encourage novel ideas and stimulate new research in the field.
血脑屏障(BBB)是一种维持脑内稳态的动态结构。血脑屏障破坏是几乎所有神经疾病的关键病理标志。尽管不同细胞对血脑屏障完整性的调节已得到广泛研究,但其非细胞成分——基膜在血脑屏障调节中的功能仍在很大程度上未知。层粘连蛋白是一种具有多种异构体的三聚体蛋白,是基膜最重要的组成成分之一。在中枢神经系统中,不同细胞合成不同的层粘连蛋白异构体,它们在生理和病理条件下对血脑屏障完整性进行不同的调节。深入了解层粘连蛋白在血脑屏障完整性中的表达和功能,可能会确定新的治疗靶点,并有可能为涉及血脑屏障破坏的神经疾病带来有效的治疗方法。在本综述中,我们首先简要介绍血脑屏障和基膜,重点是层粘连蛋白。接下来,我们以细胞特异性方式阐明层粘连蛋白在血脑屏障维持/修复中的表达及其功能。还讨论了层粘连蛋白异构体之间潜在的功能补偿。最后,总结了该领域当前的挑战和未来方向。我们的目标是提供一篇综合性综述,以鼓励新想法并激发该领域的新研究。