Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier.

Marco Tjakra,Colm Durkan,Guixue Wang,Vicki Vania,Zhengjun Hou,Nan Wang,Yeqi Wang

doi:10.3389/fnins.2019.01436

Marco Tjakra, Colm Durkan + Show 5 more

Open Access

https://doi.org/10.3389/fnins.2019.01436

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Abstract

Blood brain barrier (BBB) conserves unique regulatory system to maintain barrier tightness while allowing adequate transport between neurovascular units. This mechanism possess a challenge for drug delivery, while abnormality may result in pathogenesis. Communication between vascular and neural system is mediated through paracellular and transcellular (transcytosis) pathway. Transcytosis itself showed dependency with various components, focusing on caveolae-mediated. Among several factors, intense communication between endothelial cells, pericytes, and astrocytes is the key for a normal development. Regulatory signaling pathway such as VEGF, Notch, S1P, PDGFβ, Ang/Tie, and TGF-β showed interaction with the transcytosis steps. Recent discoveries showed exploration of various factors which has been proven to interact with one of the process of transcytosis, either endocytosis, endosomal rearrangement, or exocytosis. As well as providing a hypothetical regulatory pathway between each factors, specifically miRNA, mechanical stress, various cytokines, physicochemical, basement membrane and junctions remodeling, and crosstalk between developmental regulatory pathways. Finally, various hypotheses and probable crosstalk between each factors will be expressed, to point out relevant research application (Drug therapy design and BBB-on-a-chip) and unexplored terrain.

Highlights

Blood Brain Barrier Concept and ConstituentsThe neurovascular unit is a complex system of blood vessels and nerves, together with neighboring cells and the extracellular matrix
There have been several findings where miRNA was alternating the course of signaling pathway related to Blood brain barrier (BBB) transcytosis, mainly Vascular Endothelial Growth Factor (VEGF) (ChamorroJorganes et al, 2016), Ang/Tie (Fang et al, 2016), PDGFRβ (Tanaka et al, 2013), and TGF-beta (Zhou et al, 2016). miRNA was showed to interact with other factors concerning transcytosis, especially mechanotransduction pathway (Demolli et al, 2015) and cytokines expression (Guo et al, 2017)
By exploring factors of transcytosis which have been described above, we can apply the knowledge to the development of drug design and BBB-on-a-chip

Summary

Introduction

Blood Brain Barrier Concept and ConstituentsThe neurovascular unit is a complex system of blood vessels and nerves, together with neighboring cells and the extracellular matrix. It has been elucidated that Cav-1 plays a part in the regulation of TJ protein expression in HBMECs (Song et al, 2007), indicating a central role for the transcellular pathway in the BBB maintenance (Figure 2).

Results

Conclusion