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Tissue Non-specific Alkaline Phosphatase (TNAP) in Vessels of the Brain

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Book cover Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP)

Part of the book series: Subcellular Biochemistry ((SCBI,volume 76))

Abstract

The microvessels of the brain represent around 3–4 % of the brain compartment but constitute the most important length (400 miles) and surface of exchange (20 m2) between the blood and the parenchyma of brain. Under influence of surrounding tissues, the brain microvessel endothelium expresses a specific phenotype that regulates and restricts the entry of compounds and cells from blood to brain, and defined the so-called blood–brain barrier (BBB). Evidences that alkaline phosphatase (AP) is a characteristic feature of the BBB phenotype that allows differentiating capillary endothelial cells from brain to those of the periphery have rapidly emerge. Thenceforth, AP has been rapidly used as a biomarker of the blood-brain barrier phenotype. In fact, brain capillary endothelial cells (BCECs) express exclusively tissue non-specific alkaline phosphatase (TNAP). There are several lines of evidence in favour of an important role for TNAP in brain function. TNAP is thought to be responsible for the control of transport of some compounds across the plasma membrane of the BCECs. Here, we report that levamisole-mediated inhibition of TNAP provokes an increase of the permeability to Lucifer Yellow of the endothelial monolayer. Moreover, we illustrate the disruption of the cytoskeleton organization. Interestingly, all observed effects were reversible 24 h after levamisole removal and correlated with the return of a full activity of the TNAP. This reversible effect remains to be studied in details to evaluate the potentiality of a levamisole treatment to enhance the entry of drugs in the brain parenchyma.

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Acknowledgments

This research was funded by the Ministère de la Recherche et de l’Enseignement Supérieur. We are also grateful to Johan Hachani for his technical expertise and continuous help of every day.

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The authors declare no conflict of interest.

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Deracinois, B., Lenfant, AM., Dehouck, MP., Flahaut, C. (2015). Tissue Non-specific Alkaline Phosphatase (TNAP) in Vessels of the Brain. In: Fonta, C., Négyessy, L. (eds) Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP). Subcellular Biochemistry, vol 76. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7197-9_7

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