The blood-brain barrier, a key bridge to treat neurodegenerative diseases

Zhongci Hang; Liping Zhou; Cencan Xing; Yongqiang Wen; Hongwu Du

doi:10.1016/j.arr.2023.102070

The blood-brain barrier, a key bridge to treat neurodegenerative diseases

Ageing Res Rev. 2023 Nov:91:102070. doi: 10.1016/j.arr.2023.102070. Epub 2023 Sep 11.

Authors

Zhongci Hang¹, Liping Zhou², Cencan Xing³, Yongqiang Wen⁴, Hongwu Du⁵

Affiliations

¹ School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China.
² School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China; Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China.
³ Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China.
⁴ School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; Beijing Key Laboratory for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing 100083, China. Electronic address: wyq_wen@ustb.edu.cn.
⁵ School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China; Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China. Electronic address: hongwudu@ustb.edu.cn.

PMID: 37704051
DOI: 10.1016/j.arr.2023.102070

Abstract

As a highly selective and semi-permeable barrier that separates the circulating blood from the brain and central nervous system (CNS), the blood-brain barrier (BBB) plays a critical role in the onset and treatment of neurodegenerative diseases (NDs). To delay or reverse the NDs progression, the dysfunction of BBB should be improved to protect the brain from harmful substances. Simultaneously, a highly efficient drug delivery across the BBB is indispensable. Here, we summarized several methods to improve BBB dysfunction in NDs, including knocking out risk geneAPOE4, regulating circadian rhythms, restoring the gut microenvironment, and activating the Wnt/β-catenin signaling pathway. Then we discussed the advances in BBB penetration techniques, such as transient BBB opening, carrier-mediated drug delivery, and nasal administration, which facilitates drug delivery across the BBB. Furthermore, various in vivo and in vitro BBB models and research methods related to NDs are reviewed. Based on the current research progress, the treatment of NDs in the long term should prioritize the integrity of the BBB. However, a treatment approach that combines precise control of transient BBB permeability and non-invasive targeted BBB drug delivery holds profound significance in improving treatment effectiveness, safety, and clinical feasibility during drug therapy. This review involves the cross application of biology, materials science, imaging, engineering and other disciplines in the field of BBB, aiming to provide multi-dimensional research directions and clinical ideas for the treating NDs.

Keywords: BBB dysfunction; BBB opening; Biological guidance; Drug delivery; Neurodegenerative diseases.

Publication types

Review

MeSH terms

Blood-Brain Barrier* / metabolism
Brain / metabolism
Central Nervous System
Drug Delivery Systems
Humans
Neurodegenerative Diseases* / drug therapy
Neurodegenerative Diseases* / metabolism