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Wilson Disease: Update on Pathophysiology and Treatment

Wilson disease (WD) is a potentially fatal genetic disorder with a broad spectrum of phenotypic presentations. Inactivation of the copper (Cu) transporter ATP7B and Cu overload in tissues, especially in the liver, are established causes of WD. However, neither specific ATP7B mutations nor hepatic Cu...

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Autores principales: Dev, Som, Kruse, Robert L., Hamilton, James P., Lutsenko, Svetlana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108485/
https://www.ncbi.nlm.nih.gov/pubmed/35586338
http://dx.doi.org/10.3389/fcell.2022.871877
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author Dev, Som
Kruse, Robert L.
Hamilton, James P.
Lutsenko, Svetlana
author_facet Dev, Som
Kruse, Robert L.
Hamilton, James P.
Lutsenko, Svetlana
author_sort Dev, Som
collection PubMed
description Wilson disease (WD) is a potentially fatal genetic disorder with a broad spectrum of phenotypic presentations. Inactivation of the copper (Cu) transporter ATP7B and Cu overload in tissues, especially in the liver, are established causes of WD. However, neither specific ATP7B mutations nor hepatic Cu levels, alone, explain the diverse clinical presentations of WD. Recently, the new molecular details of WD progression and metabolic signatures of WD phenotypes began to emerge. Studies in WD patients and animal models revealed the contributions of non-parenchymal liver cells and extrahepatic tissues to the liver phenotype, and pointed to dysregulation of nuclear receptors (NR), epigenetic modifications, and mitochondria dysfunction as important hallmarks of WD pathogenesis. This review summarizes recent advances in the characterization of WD pathophysiology and discusses emerging targets for improving WD diagnosis and treatment.
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spelling pubmed-91084852022-05-17 Wilson Disease: Update on Pathophysiology and Treatment Dev, Som Kruse, Robert L. Hamilton, James P. Lutsenko, Svetlana Front Cell Dev Biol Cell and Developmental Biology Wilson disease (WD) is a potentially fatal genetic disorder with a broad spectrum of phenotypic presentations. Inactivation of the copper (Cu) transporter ATP7B and Cu overload in tissues, especially in the liver, are established causes of WD. However, neither specific ATP7B mutations nor hepatic Cu levels, alone, explain the diverse clinical presentations of WD. Recently, the new molecular details of WD progression and metabolic signatures of WD phenotypes began to emerge. Studies in WD patients and animal models revealed the contributions of non-parenchymal liver cells and extrahepatic tissues to the liver phenotype, and pointed to dysregulation of nuclear receptors (NR), epigenetic modifications, and mitochondria dysfunction as important hallmarks of WD pathogenesis. This review summarizes recent advances in the characterization of WD pathophysiology and discusses emerging targets for improving WD diagnosis and treatment. Frontiers Media S.A. 2022-05-02 /pmc/articles/PMC9108485/ /pubmed/35586338 http://dx.doi.org/10.3389/fcell.2022.871877 Text en Copyright © 2022 Dev, Kruse, Hamilton and Lutsenko. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Dev, Som
Kruse, Robert L.
Hamilton, James P.
Lutsenko, Svetlana
Wilson Disease: Update on Pathophysiology and Treatment
title Wilson Disease: Update on Pathophysiology and Treatment
title_full Wilson Disease: Update on Pathophysiology and Treatment
title_fullStr Wilson Disease: Update on Pathophysiology and Treatment
title_full_unstemmed Wilson Disease: Update on Pathophysiology and Treatment
title_short Wilson Disease: Update on Pathophysiology and Treatment
title_sort wilson disease: update on pathophysiology and treatment
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108485/
https://www.ncbi.nlm.nih.gov/pubmed/35586338
http://dx.doi.org/10.3389/fcell.2022.871877
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