Tight junction modulation at the blood-brain barrier: Current and future perspectives

Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183298. doi: 10.1016/j.bbamem.2020.183298. Epub 2020 Apr 27.

Abstract

The blood-brain barrier (BBB) is the one of the most robust physical barriers in the body, comprised of tight junction (TJ) proteins in brain microvascular endothelial cells. The need for drugs to treat central nervous systems diseases is ever increasing, however the presence of the BBB significantly hampers the uptake of drugs into the brain. To overcome or circumvent the barrier, many kinds of techniques are being developed. Modulating the paracellular route by disruption of the TJ complex has been proposed as a potential drug delivery system to treat brain diseases, however, it has several limitations and is still in a developmental stage. However, recent significant advance in medical equipment /tools such as targeted ultra-sound technologies may resolve these limitations. In this review, we introduce recent advances in site- or molecular size-selective BBB disruption/modulation technologies and we include details on pharmacological inhibitory molecules against intercellular TJ proteins to modulate the BBB.

Keywords: Blood-brain barrier; Claudin-5; Drug delivery system; Paracellular route; Tight junction.

Publication types

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

MeSH terms

  • Biological Transport / drug effects
  • Biological Transport / genetics
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Brain / blood supply
  • Brain / drug effects
  • Brain / pathology
  • Brain Diseases / drug therapy*
  • Brain Diseases / pathology
  • Central Nervous System / drug effects
  • Central Nervous System / pathology
  • Drug Delivery Systems
  • Endothelial Cells / drug effects
  • Humans
  • Permeability / drug effects
  • Tight Junction Proteins / genetics*
  • Tight Junctions / drug effects
  • Tight Junctions / genetics*

Substances

  • Tight Junction Proteins