中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (9): 1890-1902.doi: 10.4103/1673-5374.367832

• 综述:退行性病与再生 • 上一篇    下一篇

星形胶质细胞在阿尔茨海默病β淀粉样蛋白损伤后血脑屏障破坏中的新作用

  

  • 出版日期:2023-09-15 发布日期:2023-03-06

Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer’s disease

Qian Yue1, 2, Maggie Pui Man Hoi1, 2, *   

  1. 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao Special Administrative Region, China; 2Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macao Special Administrative Region, China
  • Online:2023-09-15 Published:2023-03-06
  • Contact: Maggie Pui Man Hoi, PhD, maghoi@um.edu.mo.
  • Supported by:
    This work was supported by the Science and Technology Development Fund (Macau SAR) (120015/2019/ASC, 0023/2020/AFJ, 0035/2020/AGJ) and the University of Macau Research Grant (MYRG2022-00248-ICMS) (all to MPMH).

摘要: https://orcid.org/0000-0003-2630-3707 (Maggie Pui Man Hoi) 

Abstract: Blood-brain barrier disruption occurs in the early stages of Alzheimer’s disease. Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer’s disease progression. Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier. For example, astrocytic coverage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions. Astrocyte activation is often observed in Alzheimer’s disease patients, with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta. Structural alterations in Alzheimer’s disease astrocytes including swollen endfeet, somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arterioles levels. In addition, Alzheimer’s disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration. In this review, we summarize the findings of existing literature on the relevance of astrocyte alteration in response to amyloid pathology in the context of blood-brain barrier dysfunction. First, we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance. Then, we review the clinical evidence of astrocyte pathology in Alzheimer’s disease patients and the preclinical evidence in animal and cellular models. We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer’s disease astrocyte. Finally, we evaluate the roles of soluble factors secreted by Alzheimer’s disease astrocytes, providing potential molecular mechanisms underlying blood-brain barrier modulation. We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer’s disease. 

Key words: Alzheimer’s disease, amyloid-beta, astrocyte (astroglial)-endothelial interaction, astrocyte pathology, blood-brain barrier, blood-brain barrier disruption, brain endothelial cell, neuroinflammation, reactive astrocyte