Evidence map›Paper›PMID 28011392›Full record

ArticleNeuroscience letters2017

Selective induction of P-glycoprotein at the CNS barriers during symptomatic stage of an ALS animal model.

Gary N Y Chan, Rebecca A Evans, David B Banks, Emily V Mesev, David S Miller, Ronald E Cannon

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuroscience letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.9field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Blood-CNS barrier dysfunction in amyotrophic lateral sclerosis: Proposed mechanisms and clinical implications.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Tetrabromobisphenol A (TBBPA) Alters ABC Transport at the Blood-Brain Barrier.Toxicological sciences : an official journal of the Society of Toxicology · 2019
    Article
  17. Article
  18. Thrombin and theFrontiers in neurology · 2019
    Review
  19. Review
  20. Lysophosphatidic acid and amitriptyline signal through LPA1R to reduce P-glycoprotein transport at the blood-brain barrier.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Gary N Y ChanSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States.
Rebecca A EvansSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States.
David B BanksSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States.
Emily V MesevSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States.
David S MillerSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States.
Ronald E CannonSignal Transduction Laboratory, National Institute of Environmental Health Sciences (NIEHS), 111 T.W. Alexander Drive, Research Triangle Park, NC 27709, United States. Electronic address: cannon1@niehs.nih.gov.
National Institute of Environmental Health Sciences · US

Funding

Cellular Mechanisms Of Xenobiotic TransportZIAES080048 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CANNON, RONALD E. · 2009 to 2016
$10.3M
CELLULAR MECHANISMS OF XENOBIOTIC TRANSPORTZ01ES080048 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MILLER, DAVID · 1991 to 2008
$2.0M
Intramural NIH HHS Z01 ES080048
6 · The paper itself

Abstract

P-glycoprotein (P-gp), Breast cancer resistance protein (BCRP) and Multidrug resistance-associated protein 2 (MRP2) residing at the blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) are major obstacles for drug delivery to the Central Nervous System (CNS). Disease-induced changes of these xenobiotic transporters at the CNS barriers have been previously documented. Changes in the functional expression of these transporters at the CNS barriers would limit the clinical efficacy of therapeutic agents targeting the CNS. In this study, we characterized the changes in expression and efflux activity of P-gp, BCRP and MRP2 at the BBB and BSCB of an amyotrophic lateral sclerosis (ALS) SOD1-G93A transgenic rat model across the three stages of disease progression: pre-onset, onset and symptomatic. Up-regulation of P-gp and BCRP at the BBB and BSCB during disease progression of ALS would reduce drug entry to the CNS, while any decreases in transport activity would increase drug entry. In SOD rats at the ALS symptomatic stage, we observed increases in both P-gp transport activity and expression compared to age-matched wildtypes. BCRP and MRP2 levels were unchanged in these animals. Immunohistochemical analysis in brain and spinal cord capillaries of SOD rats from all three ALS stages and age-matched wildtypes showed no differences in nuclear localization of a known P-gp regulator, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). It suggests that NFκB may have a limited role during P-gp induction observed in our study and additional signaling pathways could be responsible for this response. Our observations imply that novel pharmacological approaches for treating ALS require selecting drugs that are not P-gp substrates in order to improve therapeutic efficacy in the CNS during ALS progression.

Indexed as

Amyotrophic Lateral SclerosisAnimalsATP Binding Cassette Transporter, Subfamily B, Member 1Biological TransportBlood-Brain BarrierCentral Nervous SystemDisease Models, AnimalMembrane Transport ProteinsRatsUp-RegulationATP Binding Cassette Transporter, Subfamily B, Member 1Membrane Transport ProteinsAmyotrophic lateral sclerosisBlood-brain barrierBlood-spinal cord barrierBreast cancer resistance proteinMultidrug resistance-associated protein 2P-glycoprotein

Identifiers

PMID28011392
PMCPMC5278641
OpenAlexW2562336027

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.