Proteomic Quantification of Human Blood-Brain Barrier SLC and ABC Transporters in Healthy Individuals and Dementia Patients
Al-Majdoub ZM, Al Feteisi H, Achour B, Warwood S, Neuhoff S, Rostami-Hodjegan A, Barber J.. Molecular pharmaceutics, 2019-02-08
Topic: Brain proteins, microglia and lab models
The blood-brain barrier (BBB) maintains brain homeostasis by controlling traffic of molecules from the circulation into the brain. This function is predominantly dependent on proteins expressed at the BBB, especially transporters and tight junction proteins. Alterations to the level and function of BBB proteins can impact the susceptibility of the central nervous system to exposure to xenobiotics in the systemic circulation with potential consequent effects on brain function. In this study, expression profiles of drug transporters and solute carriers in the BBB were assessed in tissues from healthy individuals ( n = 12), Alzheimer's patients ( n = 5), and dementia with Lewy bodies patients ( n = 5), using targeted, accurate mass retention time (AMRT) and global proteomic methods. A total of 53 transporters were quantified, 19 for the first time in the BBB. A further 20 novel transporters were identified but not quantified. The global proteomic method identified another 3333 BBB proteins. Transporter abundances, taken together with the scaling factor, microvessel protein content per unit tissue (BMvPGB also measured here), can be used in quantitative systems pharmacology models predicting drug disposition in the brain and permitting dose adjustment (precision dosing) in special populations of patients, such as those with dementia. Even in this small study, we see differences in transporter profile between healthy and diseased brain tissue.
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APA 7th
Al-Majdoub, Z. M., Al Feteisi, H., Achour, B., Warwood, S., Neuhoff, S., Rostami-Hodjegan, A., et al. (2019). Proteomic Quantification of Human Blood-Brain Barrier SLC and ABC Transporters in Healthy Individuals and Dementia Patients. Molecular pharmaceutics. https://doi.org/10.1021/acs.molpharmaceut.8b01189
Vancouver
Al-Majdoub ZM, Al Feteisi H, Achour B, Warwood S, Neuhoff S, Rostami-Hodjegan A, et al. Proteomic Quantification of Human Blood-Brain Barrier SLC and ABC Transporters in Healthy Individuals and Dementia Patients. Molecular pharmaceutics. 2019. doi:10.1021/acs.molpharmaceut.8b01189. PMID: 30735053.
BibTeX
@article{almajdoub2019-30735053,
author = {Al-Majdoub, Z. M. and Al Feteisi, H. and Achour, B. and Warwood, S. and Neuhoff, S. and Rostami-Hodjegan, A. and Barber, J.},
title = {{Proteomic Quantification of Human Blood-Brain Barrier SLC and ABC Transporters in Healthy Individuals and Dementia Patients}},
journal = {Molecular pharmaceutics},
year = {2019},
doi = {10.1021/acs.molpharmaceut.8b01189},
pmid = {30735053},
url = {https://doi.org/10.1021/acs.molpharmaceut.8b01189}
}
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Key findings
- Transporter abundances, taken together with the scaling factor, microvessel protein content per unit tissue (BMvPGB also measured here), can be used in quantitative systems pharmacology models predicting drug disposition in the brain and permitting dose adjustment (precision dosing) in special populations of patients, such as those with dementia.
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Study details
- Participants12
- Evidence strengthLow
How this study scored 45/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported 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 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Molecular pharmaceutics) |
| 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 | 1 / 4 | 12 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| 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 30735053) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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