About this Research Topic

Background

Tight junctions (TJs) and transporters are essential functions to prevent unspecific diffusion and control specific exchange across the blood-brain barrier (BBB). The modulation of those functions, such as inhibition of active efflux pumps and opening TJs, are among potent strategies to enhance drug delivery to the brain. Various factors regulate the function of transporters and TJs to maintain brain homeostasis, and their regulatory mechanisms are essential information to develop functional modulators for drug delivery to the brain. Understanding the regulations is also necessary to prevent the unpreferable enhancement of systemic drug distribution in the brain, leading to CNS side effects.


The molecular mechanisms of transporter and TJ regulation at the BBB are still poorly understood to be utilized for the development of drug delivery to the brain. Various in vitro BBB models, such as iPSC-derived models and 3D cultures, have been developed. Omics analysis and screening provide new molecular insights by unbiased approaches. Those recent advances in methodologies will contribute to identifying novel molecular mechanisms of the regulation of transporters and TJs at the BBB to help develop novel drug delivery strategies and understand drug distribution to the brain.

The scope of this research topic includes the molecular mechanisms of functional regulation of BBB transporters, such as MDR1, BCRP and LAT1, and modulators for those transporters to enhance drug distribution to the brain. The topic also includes the molecular mechanisms of TJ integrity and the expression and subcellular localization of TJ proteins, and methodology to modulate TJ integrity, such as peptides, antibodies, siRNA or ultrasound, to facilitate drug delivery.

Submissions are welcome for the following article types: original research, review, mini-reviews, re-search protocol/method, opinion and hypothesis.

Keywords: ABC Transporter, SLC Transporter, Receptor Mediated Transcytosis, Adsorptive Mediated Transcytosis, Tight Junctions, Claudins, Occludin

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