4.7 Review

Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease

Related references

Note: Only part of the references are listed.
Article Genetics & Heredity

Atp7b-dependent choroid plexus dysfunction Causes transient copper deficit and metabolic changes in the developing mouse brain

Clorissa L. Washington-Hughes et al.

Summary: This study reveals the importance of Cu transporter Atp7b in maintaining Cu homeostasis in the brain during postnatal development. Loss of Atp7b function leads to morphological changes in choroid plexus and affects Cu transporters Atp7a and Slc31a, resulting in Cu deficit and associated imbalance of catecholamines and lipids. These findings contribute to our understanding of the neuropathology of Wilson disease.

PLOS GENETICS (2023)

Article Gastroenterology & Hepatology

A multidisciplinary approach to the diagnosis and management of Wilson disease: Executive summary of the 2022 Practice Guidance on Wilson disease from the American Association for the Study of Liver Diseases

Michael L. Schilsky et al.

Summary: This is an executive summary of the extensively rewritten guidance on the diagnosis and management of Wilson disease. The full guidance document can be found on the American Association for the Study of Liver Diseases (AASLD) website. The summary provides an overview and guidance statements based on evidence and expert consensus opinion.

HEPATOLOGY (2023)

Article Gastroenterology & Hepatology

ARBM101 (Methanobactin SB2) Drains Excess Liver Copper via Biliary Excretion in Wilson's Disease Rats

Claudia Einer et al.

Summary: This study tested the efficiency and safety of bacteria-derived copper binding agents (MBs) in depleting excess copper from the livers of WD rats, and found that a copper-binding agent called ARBM101 can effectively deplete liver copper to normal levels within 8 days. They developed a new treatment approach consisting of repetitive cycles of ARBM101 applications followed by rest periods to ensure long-term survival in WD rats.

GASTROENTEROLOGY (2023)

Article Pathology

Hepatic Steatosis in the Mouse Model of Wilson Disease Coincides with a Muted Inflammatory Response

Aline Gottlieb et al.

Summary: Wilson disease is caused by inactivation of the copper transporter ATP7B and diet has an impact on liver phenotype in Wilson disease patients. Despite elevated hepatic copper levels, liver inflammation was reduced in high calorie diet conditions, causing changes in cellular pathways.

AMERICAN JOURNAL OF PATHOLOGY (2022)

Article Cell Biology

Discovery of farnesoid X receptor and its role in bile acid metabolism

John Y. L. Chiang et al.

Summary: This article introduces the discovery of FXR as a regulator of bile acid metabolism and a metabolic regulator of lipid, glucose, and energy homeostasis. It also provides an update on FXR functions in the gut-to-liver axis and the use of drug therapies targeting bile acids and FXR for the treatment of liver metabolic diseases.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2022)

Article Multidisciplinary Sciences

Copper induces cell death by targeting lipoylated TCA cycle proteins

Peter Tsvetkov et al.

Summary: Copper is an essential cofactor for all organisms, but excessive copper can lead to cell death. We found that copper-dependent cell death mechanism is different from known mechanisms, and it is related to mitochondrial respiration. Copper directly binds to lipoylated components of the tricarboxylic acid cycle, causing protein aggregation and loss of iron-sulfur cluster proteins, ultimately leading to cell death.

SCIENCE (2022)

Article Cell Biology

Recent advances on FXR-targeting therapeutics

Katrin Panzitt et al.

Summary: The bile acid receptor FXR is considered as an important drug target for chronic cholestatic and metabolic liver diseases. Activation of FXR in the liver and intestine has different effects on metabolism. There is still debate about whether selective activation of intestinal FXR is advantageous and how to limit FXR activation to reduce side effects.

MOLECULAR AND CELLULAR ENDOCRINOLOGY (2022)

Review Medicine, Research & Experimental

A new perspective on NAFLD: Focusing on the crosstalk between peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR)

Shipeng Zhou et al.

Summary: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease primarily caused by abnormal lipid metabolism and triglyceride accumulation in the liver. Nuclear receptors PPARα and FXR play a crucial role in the pathogenesis of NAFLD and are considered the most promising targets for treatment.

BIOMEDICINE & PHARMACOTHERAPY (2022)

Article Biochemistry & Molecular Biology

Lipid-related metabolism during zebrafish embryogenesis under unbalanced copper homeostasis

ChangShun Li et al.

Summary: This study investigated the effects of Cu overload and ATP7A, ATP7B inactivation on lipid metabolism-related genes in zebrafish disease models, revealing their dynamic and spatiotemporal expression patterns during zebrafish development. The findings provide important insights for vertebrate embryonic development and lipid metabolism disorders.

FISH PHYSIOLOGY AND BIOCHEMISTRY (2022)

Article Multidisciplinary Sciences

Oxysterol misbalance critically contributes to Wilson disease pathogenesis

Som Dev et al.

Summary: This study identified an important regulatory pathway in Wilson disease with copper metabolism abnormalities, which can improve liver damage and restore function.

SCIENCE ADVANCES (2022)

Review Biochemistry & Molecular Biology

Toxic milk mice models of Wilson's disease

Krzysztof Hadrian et al.

Summary: The two strains of toxic milk mice (tx and txJ) exhibit different genetic mutations and disease phenotypes. The tx mice developed mild chronic hepatitis with rapid progression to full-liver cirrhosis, while the txJ mice had a milder form of chronic hepatitis with slower disease progression. The neurological and behavioral characteristics of the two strains also differ, with the txJ mice more closely resembling the clinical neurological presentation in humans.

MOLECULAR BIOLOGY REPORTS (2021)

Article Multidisciplinary Sciences

Systemic deletion of Atp7b modifies the hepatocytes' response to copper overload in the mouse models of Wilson disease

Abigael Muchenditsi et al.

Summary: The study found that global inactivation of Atp7b enhances and specifically modifies the hepatocyte response to copper overload, while the loss of Atp7b only in hepatocytes causes dysregulation of lipid and nucleic acid metabolism.

SCIENTIFIC REPORTS (2021)

Article Gastroenterology & Hepatology

Wilson Disease: Intersecting DNA Methylation and Histone Acetylation Regulation of Gene Expression in a Mouse Model of Hepatic Copper Accumulation

Gaurav Sarode et al.

Summary: The study reveals that the pathogenesis of Wilson disease involves copper accumulation in the liver and brain, affecting acetylation levels through changes in histone deacetylase 5. Dietary modulation can regulate the acetylation levels of HDAC4/5 and H3K9/H3K27.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2021)

Article Gastroenterology & Hepatology

The Prevalence of Wilson's Disease: An Update

Thomas Damgaard Sandahl et al.

HEPATOLOGY (2020)

Article Multidisciplinary Sciences

Metabolic dysregulation in the Atp7b-/- Wilson's disease mouse model

Clavia Ruth Wooton-Kee et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

Article Multidisciplinary Sciences

SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis

Jiyu Zhou et al.

NATURE COMMUNICATIONS (2020)

Article Biochemistry & Molecular Biology

Activation of HIF-1 signaling ameliorates liver steatosis in zebrafish atp7b deficiency (Wilson's disease) models

Xiaoxiao Mi et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2020)

Article Endocrinology & Metabolism

Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature

Gaurav V. Sarode et al.

METABOLOMICS (2019)

Review Oncology

Preclinical models of Wilson's disease, why dogs are catchy alternatives

Hedwig S. Kruitwagen et al.

ANNALS OF TRANSLATIONAL MEDICINE (2019)

Article Veterinary Sciences

Reduced FXR Target Gene Expression in Copper-Laden Livers of COMMD1-Deficient Dogs

Xiaoyan Wu et al.

VETERINARY SCIENCES (2019)

Article Gastroenterology & Hepatology

A High-Calorie Diet Aggravates Mitochondrial Dysfunction and Triggers Severe Liver Damage in Wilson Disease Rats

Claudia Einer et al.

CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2019)

Article Gastroenterology & Hepatology

The Function of ATPase Copper Transporter ATP7B in Intestine

Hannah Pierson et al.

GASTROENTEROLOGY (2018)

Review Endocrinology & Metabolism

Liver X receptors in lipid signalling and membrane homeostasis

Bo Wang et al.

NATURE REVIEWS ENDOCRINOLOGY (2018)

Review Endocrinology & Metabolism

Fibroblast Growth Factor 15/19: From Basic Functions to Therapeutic Perspectives

Emmanuel Somm et al.

ENDOCRINE REVIEWS (2018)

Article Gastroenterology & Hepatology

Targeted inactivation of copper transporter Atp7b in hepatocytes causes liver steatosis and obesity in mice

Abigael Muchenditsi et al.

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY (2017)

Article Medicine, Research & Experimental

Methanobactin reverses acute liver failure in a rat model of Wilson disease

Josef Lichtmannegger et al.

JOURNAL OF CLINICAL INVESTIGATION (2016)

Article Medicine, Research & Experimental

Elevated copper impairs hepatic nuclear receptor function in Wilson's disease

Clavia Ruth Wooton-Kee et al.

JOURNAL OF CLINICAL INVESTIGATION (2015)

Article Endocrinology & Metabolism

New canine models of copper toxicosis: diagnosis, treatment, and genetics

Hille Fieten et al.

HUMAN DISORDERS OF COPPER METABOLISM I (2014)

Article Biochemistry & Molecular Biology

Nuclear Receptors HNF4α and LRH-1 Cooperate in Regulating Cyp7a1 in Vivo

Serkan Kir et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2012)

Article Biochemistry & Molecular Biology

A systems approach implicates nuclear receptor targeting in the Atp7b-/- mouse model of Wilson's disease

Phillip A. Wilmarth et al.

METALLOMICS (2012)

Article Medicine, Research & Experimental

Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease

Hans Zischka et al.

JOURNAL OF CLINICAL INVESTIGATION (2011)

Article Biochemistry & Molecular Biology

Structural and thermodynamic consequences of the replacement of zinc with environmental metals on estrogen receptor α-DNA interactions

Brian J. Deegan et al.

JOURNAL OF MOLECULAR RECOGNITION (2011)

Review Biochemistry & Molecular Biology

Bile acids: regulation of synthesis

John Y. L. Chiang

JOURNAL OF LIPID RESEARCH (2009)

Article Endocrinology & Metabolism

Mitochondrial structure and function in the untreated Jackson toxic milk (tx-j) mouse, a model for Wilson disease

Eve A. Roberts et al.

MOLECULAR GENETICS AND METABOLISM (2008)

Article Multidisciplinary Sciences

Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer

Lucia Banci et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Article Biochemistry & Molecular Biology

Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine

Insook Kim et al.

JOURNAL OF LIPID RESEARCH (2007)

Article Genetics & Heredity

Sequence variation database for the Wilson disease copper transporter, ATP7B

Susan M. Kenney et al.

HUMAN MUTATION (2007)

Review Physiology

Function and regulation of human copper-transporting ATPases

Svetlana Lutsenko et al.

PHYSIOLOGICAL REVIEWS (2007)

Article Biochemistry & Molecular Biology

High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease

Dominik Huster et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2007)

Article Gastroenterology & Hepatology

The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease

Mario Lovicu et al.

JOURNAL OF GASTROENTEROLOGY (2006)

Article Gastroenterology & Hepatology

Copper toxicosis gene MURR1 is not changed in Wilson disease patients with normal blood ceruloplasmin levels

Karl Heinz Weiss et al.

WORLD JOURNAL OF GASTROENTEROLOGY (2006)

Article Medicine, Research & Experimental

Farnesoid X receptor is essential for normal glucose homeostasis

K Ma et al.

JOURNAL OF CLINICAL INVESTIGATION (2006)

Article Gastroenterology & Hepatology

ATP7B mediates vesicular sequestration of copper: Insight into biliary copper excretion

MA Cater et al.

GASTROENTEROLOGY (2006)

Article Neurosciences

A new strain of rat for functional analysis of PINA

S Ahmed et al.

MOLECULAR BRAIN RESEARCH (2005)

Article Genetics & Heredity

Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients

B Stuehler et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2004)

Article Gastroenterology & Hepatology

Liver cirrhosis and metabolism (sugar, protein, fat and trace elements)

Y Arakawa et al.

HEPATOLOGY RESEARCH (2004)

Article Biochemistry & Molecular Biology

The Jackson toxic milk mouse as a model for copper loading

V Coronado et al.

MAMMALIAN GENOME (2001)

Article Biochemistry & Molecular Biology

Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor

M Ananthanarayanan et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2001)

Article Medicine, General & Internal

Oxidative-phosphorylation defects in liver of patients with Wilson's disease

M Gu et al.

LANCET (2000)