Evidence map›Paper›PMID 27158936›Full record

ArticleGlia2016

Astrocytes drive upregulation of the multidrug resistance transporter ABCB1 (P-Glycoprotein) in endothelial cells of the blood-brain barrier in mutant superoxide dismutase 1-linked amyotrophic lateral sclerosis.

Hisham Qosa, Jessica Lichter, Mark Sarlo, Shashirekha S Markandaiah, Kevin McAvoy, Jean-Philippe Richard, Michael R Jablonski, Nicholas J Maragakis, Piera Pasinelli, Davide Trotti

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Glia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

47 citing papers in PubMed, 70 citations in OpenAlex.

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  12. 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
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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

10 authors at 3 institutions in 1 country.

Hisham QosaJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Jessica LichterJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Mark SarloJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Shashirekha S MarkandaiahJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Kevin McAvoyJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Jean-Philippe RichardDepartment of Neurology, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland.
Michael R JablonskiJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Nicholas J MaragakisDepartment of Neurology, Johns Hopkins University School of Medicine, 855 N. Wolfe Street, Baltimore, Maryland.
Piera PasinelliJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Davide TrottiJefferson Weinberg ALS Center, Vickie and Jack Farber Institute for Neuroscience, Department of Neuroscience, Thomas Jefferson University, 900 Walnut Street, Philadelphia, Pennsylvania.
Thomas Jefferson University · USJefferson Hospital for Neuroscience · USJohns Hopkins University · US

Funding

Role of ABC efflux transporters in ALSR01NS074886 · NINDS · THOMAS JEFFERSON UNIVERSITY · PI TROTTI, DAVIDE · 2011 to 2015
$1.7M
NINDS NIH HHS R01 NS074886
6 · The paper itself

Abstract

The efficacy of drugs targeting the CNS is influenced by their limited brain access, which can lead to complete pharmacoresistance. Recently a tissue-specific and selective upregulation of the multidrug efflux transporter ABCB1 or P-glycoprotein (P-gp) in the spinal cord of both patients and the mutant SOD1-G93A mouse model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that prevalently kills motor neurons has been reported. Here, we extended the analysis of P-gp expression in the SOD1-G93A ALS mouse model and found that P-gp upregulation was restricted to endothelial cells of the capillaries, while P-gp expression was not detected in other cells of the spinal cord parenchyma such as astrocytes, oligodendrocytes, and neurons. Using both in vitro human and mouse models of the blood-brain barrier (BBB), we found that mutant SOD1 astrocytes were driving P-gp upregulation in endothelial cells. In addition, a significant increase in reactive oxygen species production, Nrf2 and NFκB activation in endothelial cells exposed to mutant SOD1 astrocytes in both human and murine BBB models were observed. Most interestingly, astrocytes expressing FUS-H517Q, a different familial ALS-linked mutated gene, also drove NFκB-dependent upregulation of P-gp. However, the pathway was not dependent on oxidative stress but rather involved TNF-α release. Overall, these findings indicated that nuclear translocation of NFκB was a converging mechanism used by endothelial cells of the BBB to upregulate P-gp expression in mutant SOD1-linked ALS and possibly other forms of familial ALS. GLIA 2016 GLIA 2016;64:1298-1313.

Indexed as

Amyotrophic Lateral SclerosisAnimalsAstrocytesATP-Binding Cassette Sub-Family B Member 4ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Blood-Brain BarrierCapillariesCell LineCoculture TechniquesDisease Models, AnimalEndothelial CellsHumansInduced Pluripotent Stem CellsMice, TransgenicNF-kappa BABCB1 protein, humanATP-Binding Cassette Sub-Family B Member 4ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1FUS protein, humanFUS protein, mouseNF-kappa BRNA-Binding Protein FUSSOD1 protein, humanSuperoxide Dismutase-1amyotrophic lateral sclerosisblood-brain barrierendothelial cellsmutant SOD1P-glycoprotein

Identifiers

PMID27158936
PMCPMC5541958
OpenAlexW2362681544

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.