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Updated: Dec 20, 2025

Systemic and Local Drug Delivery for Treating Diseases of the Central Nervous System in Rodent Models
Published on: August 16, 2010
Tight junction modulators for drug delivery to the central nervous system
Yosuke Hashimoto1, Keisuke Tachibana2, Masuo Kondoh2
1Neurovascular Genetics Laboratory, Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
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.
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