Tight junction modulators for drug delivery to the central nervous system

Yosuke Hashimoto; Keisuke Tachibana; Masuo Kondoh

doi:10.1016/j.drudis.2020.05.007

Tight junction modulators for drug delivery to the central nervous system

Drug Discov Today. 2020 Aug;25(8):1477-1486. doi: 10.1016/j.drudis.2020.05.007. Epub 2020 May 18.

Authors

Yosuke Hashimoto¹, Keisuke Tachibana², Masuo Kondoh³

Affiliations

¹ Neurovascular Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
² Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
³ Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan. Electronic address: masuo@phs.osaka-u.ac.jp.

PMID: 32439607
DOI: 10.1016/j.drudis.2020.05.007

Abstract

Overcoming the blood-brain barrier (BBB) to enable the treatment of central nervous system (CNS) diseases is an active field of research. Modulating or opening the tight junctions (TJs) in brain endothelial cells is one method to enable a range of small-molecular-weight drugs to cross the BBB via the paracellular route. Over the past 2 decades, the molecular understanding of TJ proteins in the BBB has significantly improved, and several agonists and antagonists have been tested for modulation of the TJs. In this review, we discuss the composition of TJ proteins in the BBB and introduce indirect pharmacological TJ modulators, which target regulators of TJ proteins, and direct TJ modulators, which can selectively inhibit functions of TJ proteins.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Brain / metabolism*
Drug Delivery Systems*
Endothelial Cells / metabolism
Humans
Tight Junction Proteins / metabolism
Tight Junctions / metabolism*

Substances

Tight Junction Proteins