3.8 Article

Proteome of the Luminal Surface of the Blood-Brain Barrier

Journal

PROTEOMES
Volume 9, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/proteomes9040045

Keywords

blood-brain barrier; luminal; proteomics; brain endothelial cells; receptor-mediated transcytosis

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Proteomic techniques have provided insights into the unique protein organization at the blood-brain barrier, particularly focusing on cellular components and transport mechanisms. In vivo proteomics approaches involve capturing luminal proteins for analysis using mass spectrometry-based methods, contributing to the development of novel delivery methods across the BBB.
Interrogation of the molecular makeup of the blood-brain barrier (BBB) using proteomic techniques has contributed to the cataloguing and functional understanding of the proteins uniquely organized at this specialized interface. The majority of proteomic studies have focused on cellular components of the BBB, including cultured brain endothelial cells (BEC). Detailed proteome mapping of polarized BEC membranes and their intracellular endosomal compartments has led to an improved understanding of the processes leading to internalization and transport of various classes of molecules across the BBB. Quantitative proteomic methods have further enabled absolute and comparative quantification of key BBB transporters and receptors in isolated BEC and microvessels from various species. However, translational studies further require in vivo/in situ analyses of the proteins exposed on the luminal surface of BEC in vessels under various disease and treatment conditions. In vivo proteomics approaches, both profiling and quantitative, usually rely on 'capturing' luminally-exposed proteins after perfusion with chemical labeling reagents, followed by analysis with various mass spectrometry-based approaches. This manuscript reviews recent advances in proteomic analyses of luminal membranes of BEC in vitro and in vivo and their applications in translational studies focused on developing novel delivery methods across the BBB.

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