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Cited by 583Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsIon Transport and Channel Regulation

Claudin-5: gatekeeper of neurological function

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Greene, Chris, Hanley, Nicole, Campbell, Matthew·2019·Fluids and Barriers of the CNS
DOI 10.1186/s12987-019-0123-zPMC PMC6350359
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Abstract

Tight junction proteins of the blood-brain barrier are vital for maintaining integrity of endothelial cells lining brain blood vessels. The presence of these protein complexes in the space between endothelial cells creates a dynamic, highly regulated and restrictive microenvironment that is vital for neural homeostasis. By limiting paracellular diffusion of material between blood and brain, tight junction proteins provide a protective barrier preventing the passage of unwanted and potentially damaging material. Simultaneously, this protective barrier hinders the therapeutic effectiveness of central nervous system acting drugs with over 95% of small molecule therapeutics unable to bypass the blood-brain barrier. At the blood-brain barrier, claudin-5 is the most enriched tight junction protein and its dysfunction has been implicated in neurodegenerative disorders such as Alzheimer's disease, neuroinflammatory disorders such as multiple sclerosis as well as psychiatric disorders including depression and schizophrenia. By regulating levels of claudin-5, it is possible to abrogate disease symptoms in many of these disorders. This review will give an overview of the blood-brain barrier and the role of tight junction complexes in maintaining blood-brain barrier integrity before focusing on the role of claudin-5 and its regulation in homeostatic and pathological conditions. We will also summarise therapeutic strategies to restore integrity of cerebral vessels by targeting tight junction protein complexes.

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Cited by

Sorted by citations

Authors
Greene, C., Hanley, N., & Campbell, M.
Affiliations
Trinity College Dublin (IE)
Corresponding author
Campbell, Matthew
ORCID
Venue
Fluids and Barriers of the CNS
Publisher
Springer Science and Business Media LLC
Published
2019-01-29
Volume
16
Issue
1
Pages
3-3
ISSN
2045-8118 (ISSN-L)
DOI
10.1186/s12987-019-0123-z
PMC
PMC6350359
OpenAlex
W2928956234
Cited by
583
References
18
Citations by year
2026: 99 · 2025: 115 · 2024: 85 · 2023: 82 · 2022: 69 · 2021: 73 · 2020: 49 · 2019: 11
FWCI
5.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Fluids and Barriers of the CNS (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
  • BrightFocus Foundation (16/RC/3948)
  • Health Research Board (HRA-POR-2015-1077)
  • Enterprise Ireland
  • Science Foundation Ireland (11/PI/1080, 16/RC/3948)
  • European Regional Development Fund (16/RC/3948)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
claudin-5, blood-brain barrier, tight junction proteins, endothelial cells, paracellular diffusion, blood-brain barrier permeability, brain drug delivery, Alzheimer's disease, multiple sclerosis, depression, schizophrenia, tight junction regulation
MeSH terms
Animals, Blood-Brain Barrier, Humans, Claudin-5

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