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Claudin-5: gatekeeper of neurological function
Greene C, Hanley N, Campbell M.. Fluids and barriers of the CNS, 2019-01-29
Topic: Inflammation, microglia and astrocytes
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.
Key findings
- 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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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Fluids and barriers of the CNS) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30691500) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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APA 7th
Greene, C., Hanley, N., & Campbell, M. (2019). Claudin-5: gatekeeper of neurological function. Fluids and barriers of the CNS. https://doi.org/10.1186/s12987-019-0123-z
Vancouver
Greene C, Hanley N, Campbell M. Claudin-5: gatekeeper of neurological function. Fluids and barriers of the CNS. 2019. doi:10.1186/s12987-019-0123-z. PMID: 30691500.
BibTeX
@article{greene2019-30691500,
author = {Greene, C. and Hanley, N. and Campbell, M.},
title = {{Claudin-5: gatekeeper of neurological function}},
journal = {Fluids and barriers of the CNS},
year = {2019},
doi = {10.1186/s12987-019-0123-z},
pmid = {30691500},
url = {https://doi.org/10.1186/s12987-019-0123-z}
}