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Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients
For amyotrophic lateral sclerosis (ALS), achieving and maintaining effective drug levels in the brain is challenging due to the activity of ATP-binding cassette (ABC) transporters which efflux drugs that affect drug exposure and response in the brain. We investigated the expression and cellular dist...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036662/ https://www.ncbi.nlm.nih.gov/pubmed/31999342 http://dx.doi.org/10.1093/jnen/nlz142 |
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author | van Vliet, Erwin A Iyer, Anand M Mesarosova, Lucia Çolakoglu, Hilal Anink, Jasper J van Tellingen, Olaf Maragakis, Nicholas J Shefner, Jeremy Bunt, Ton Aronica, Eleonora |
author_facet | van Vliet, Erwin A Iyer, Anand M Mesarosova, Lucia Çolakoglu, Hilal Anink, Jasper J van Tellingen, Olaf Maragakis, Nicholas J Shefner, Jeremy Bunt, Ton Aronica, Eleonora |
author_sort | van Vliet, Erwin A |
collection | PubMed |
description | For amyotrophic lateral sclerosis (ALS), achieving and maintaining effective drug levels in the brain is challenging due to the activity of ATP-binding cassette (ABC) transporters which efflux drugs that affect drug exposure and response in the brain. We investigated the expression and cellular distribution of the ABC transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) using immunohistochemistry in spinal cord (SC), motor cortex, and cerebellum from a large cohort of genetically well characterized ALS patients (n = 25) and controls (n = 14). The ALS group included 17 sporadic (sALS) and 8 familial (fALS) patients. Strong P-gp expression was observed in endothelial cells in both control and ALS specimens. Immunohistochemical analysis showed higher P-gp expression in reactive astroglial cells in both gray (ventral horn) and white matter of the SC, as well as in the motor cortex of all ALS patients, as compared with controls. BCRP expression was higher in glia in the SC and in blood vessels and glia in the motor cortex of ALS patients, as compared with controls. P-gp and BCRP immunoreactivity did not differ between sALS and fALS cases. The upregulation of both ABC transporters in the brain may explain multidrug resistance in ALS patients and has implications for the use of both approved and experimental therapeutics. |
format | Online Article Text |
id | pubmed-7036662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70366622020-03-02 Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients van Vliet, Erwin A Iyer, Anand M Mesarosova, Lucia Çolakoglu, Hilal Anink, Jasper J van Tellingen, Olaf Maragakis, Nicholas J Shefner, Jeremy Bunt, Ton Aronica, Eleonora J Neuropathol Exp Neurol Original Articles For amyotrophic lateral sclerosis (ALS), achieving and maintaining effective drug levels in the brain is challenging due to the activity of ATP-binding cassette (ABC) transporters which efflux drugs that affect drug exposure and response in the brain. We investigated the expression and cellular distribution of the ABC transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) using immunohistochemistry in spinal cord (SC), motor cortex, and cerebellum from a large cohort of genetically well characterized ALS patients (n = 25) and controls (n = 14). The ALS group included 17 sporadic (sALS) and 8 familial (fALS) patients. Strong P-gp expression was observed in endothelial cells in both control and ALS specimens. Immunohistochemical analysis showed higher P-gp expression in reactive astroglial cells in both gray (ventral horn) and white matter of the SC, as well as in the motor cortex of all ALS patients, as compared with controls. BCRP expression was higher in glia in the SC and in blood vessels and glia in the motor cortex of ALS patients, as compared with controls. P-gp and BCRP immunoreactivity did not differ between sALS and fALS cases. The upregulation of both ABC transporters in the brain may explain multidrug resistance in ALS patients and has implications for the use of both approved and experimental therapeutics. Oxford University Press 2020-03 2019-12-27 /pmc/articles/PMC7036662/ /pubmed/31999342 http://dx.doi.org/10.1093/jnen/nlz142 Text en © 2019 American Association of Neuropathologists, Inc. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles van Vliet, Erwin A Iyer, Anand M Mesarosova, Lucia Çolakoglu, Hilal Anink, Jasper J van Tellingen, Olaf Maragakis, Nicholas J Shefner, Jeremy Bunt, Ton Aronica, Eleonora Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients |
title | Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients |
title_full | Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients |
title_fullStr | Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients |
title_full_unstemmed | Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients |
title_short | Expression and Cellular Distribution of P-Glycoprotein and Breast Cancer Resistance Protein in Amyotrophic Lateral Sclerosis Patients |
title_sort | expression and cellular distribution of p-glycoprotein and breast cancer resistance protein in amyotrophic lateral sclerosis patients |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036662/ https://www.ncbi.nlm.nih.gov/pubmed/31999342 http://dx.doi.org/10.1093/jnen/nlz142 |
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