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Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage
In Wilson disease, excessive copper accumulates in patients’ livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675913/ https://www.ncbi.nlm.nih.gov/pubmed/34857647 http://dx.doi.org/10.26508/lsa.202101164 |
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author | Borchard, Sabine Raschke, Stefanie Zak, Krzysztof M Eberhagen, Carola Einer, Claudia Weber, Elisabeth Müller, Sandra M Michalke, Bernhard Lichtmannegger, Josef Wieser, Albrecht Rieder, Tamara Popowicz, Grzegorz M Adamski, Jerzy Klingenspor, Martin Coles, Andrew H Viana, Ruth Vendelbo, Mikkel H Sandahl, Thomas D Schwerdtle, Tanja Plitz, Thomas Zischka, Hans |
author_facet | Borchard, Sabine Raschke, Stefanie Zak, Krzysztof M Eberhagen, Carola Einer, Claudia Weber, Elisabeth Müller, Sandra M Michalke, Bernhard Lichtmannegger, Josef Wieser, Albrecht Rieder, Tamara Popowicz, Grzegorz M Adamski, Jerzy Klingenspor, Martin Coles, Andrew H Viana, Ruth Vendelbo, Mikkel H Sandahl, Thomas D Schwerdtle, Tanja Plitz, Thomas Zischka, Hans |
author_sort | Borchard, Sabine |
collection | PubMed |
description | In Wilson disease, excessive copper accumulates in patients’ livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840), the latter with a very high copper affinity. Hence, ALXN1840 may potentially avoid neurological deterioration that frequently occurs upon DPA treatment. As the etiology of such worsening is unclear, we reasoned that copper loosely bound to albumin, that is, mimicking a potential liver copper leakage into blood, may damage cells that constitute the blood-brain barrier, which was found to be the case in an in vitro model using primary porcine brain capillary endothelial cells. Such blood–brain barrier damage was avoided by ALXN1840, plausibly due to firm protein embedding of the chelator bound copper, but not by DPA. Mitochondrial protection was observed, a prerequisite for blood–brain barrier integrity. Thus, high-affinity copper chelators may minimize such deterioration in the treatment of neurologic Wilson disease. |
format | Online Article Text |
id | pubmed-8675913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-86759132022-01-05 Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage Borchard, Sabine Raschke, Stefanie Zak, Krzysztof M Eberhagen, Carola Einer, Claudia Weber, Elisabeth Müller, Sandra M Michalke, Bernhard Lichtmannegger, Josef Wieser, Albrecht Rieder, Tamara Popowicz, Grzegorz M Adamski, Jerzy Klingenspor, Martin Coles, Andrew H Viana, Ruth Vendelbo, Mikkel H Sandahl, Thomas D Schwerdtle, Tanja Plitz, Thomas Zischka, Hans Life Sci Alliance Research Articles In Wilson disease, excessive copper accumulates in patients’ livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840), the latter with a very high copper affinity. Hence, ALXN1840 may potentially avoid neurological deterioration that frequently occurs upon DPA treatment. As the etiology of such worsening is unclear, we reasoned that copper loosely bound to albumin, that is, mimicking a potential liver copper leakage into blood, may damage cells that constitute the blood-brain barrier, which was found to be the case in an in vitro model using primary porcine brain capillary endothelial cells. Such blood–brain barrier damage was avoided by ALXN1840, plausibly due to firm protein embedding of the chelator bound copper, but not by DPA. Mitochondrial protection was observed, a prerequisite for blood–brain barrier integrity. Thus, high-affinity copper chelators may minimize such deterioration in the treatment of neurologic Wilson disease. Life Science Alliance LLC 2021-12-02 /pmc/articles/PMC8675913/ /pubmed/34857647 http://dx.doi.org/10.26508/lsa.202101164 Text en © 2021 Borchard et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Borchard, Sabine Raschke, Stefanie Zak, Krzysztof M Eberhagen, Carola Einer, Claudia Weber, Elisabeth Müller, Sandra M Michalke, Bernhard Lichtmannegger, Josef Wieser, Albrecht Rieder, Tamara Popowicz, Grzegorz M Adamski, Jerzy Klingenspor, Martin Coles, Andrew H Viana, Ruth Vendelbo, Mikkel H Sandahl, Thomas D Schwerdtle, Tanja Plitz, Thomas Zischka, Hans Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
title | Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
title_full | Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
title_fullStr | Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
title_full_unstemmed | Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
title_short | Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
title_sort | bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675913/ https://www.ncbi.nlm.nih.gov/pubmed/34857647 http://dx.doi.org/10.26508/lsa.202101164 |
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