中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (12): 2557-2563.doi: 10.4103/1673-5374.373677

• 综述:退行性病与再生 •    下一篇

成人发病的神经退行性阿尔茨海默病与生命早期神经退行性神经元蜡样脂褐质症之间的融合联系?

  

  • 出版日期:2023-12-15 发布日期:2023-06-13

The importance of laminin at the blood-brain barrier

Sebok K. Halder, Arjun Sapkota, Richard Milner*   

  1. San Diego Biomedical Research Institute, San Diego, CA, USA
  • Online:2023-12-15 Published:2023-06-13
  • Contact: Richard Milner, MD, PhD, rmilner@sdbri.org.
  • Supported by:
    This work was supported by the NIH RO1, No. NS103966 (to RM).

摘要: https://orcid.org/0000-0002-3327-3609 (Richard Milner)

Abstract: The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components. The mechanistic basis of this barrier is found at multiple levels, including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes, microglia, and astrocyte endfeet. In addition, extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity, not only by providing an adhesive substrate for blood-brain barrier cells to adhere to, but also by providing guidance cues that strongly influence vascular cell behavior. The extracellular matrix protein laminin is one of the most abundant components of the basement membrane, and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior. In this review, we describe the basic structure of laminin and its receptors, the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states, and most importantly, how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity. Finally, we discuss some of the important unanswered questions in the field and provide a “to-do” list of some of the critical outstanding experiments. 

Key words: astrocytes, basement membrane, blood vessels, blood-brain barrier integrity, dystroglycan, endothelial cells, inflammation, integrins, laminin, pericytes