Review
Biochemistry & Molecular Biology
Nina Horn, Pernilla Wittung-Stafshede
Summary: Copper is essential for cellular functions, with ATP7A playing a critical role in copper balance. Dysfunction of ATP7A leads to Menkes disease, characterized by copper deficiency and accumulation in different tissues. Studying the roles of copper enzymes in Menkes disease can provide insights into disease mechanisms and improve early diagnosis accuracy.
Article
Clinical Neurology
Daniel Natera-de Benito, Abel Sola, Paulo Rego Sousa, Susana Boronat, Jessica Exposito-Escudero, Laura Carrera-Garcia, Carlos Ortez, Cristina Jou, Jordi Muchart, Monica Rebollo, Judith Armstrong, Jaume Colomer, Angels Garcia-Cazorla, Janet Hoenicka, Francesc Palau, Andres Nascimento
Summary: The study identified a novel ATP7A mutation in a family with OHS, along with a patient who developed severe worsening of dHMN after copper histidinate treatment. Functional studies showed high levels of superoxide ion in the patient's mitochondria, along with low expression levels of ATP7A and ATP7B.
PEDIATRIC NEUROLOGY
(2021)
Article
Neurosciences
Lisbeth Birk Moller, Mie Mogensen, David D. Weaver, Per Amstrup Pedersen
Summary: Disease-causing variants in ATP7A result in Menkes disease and occipital horn syndrome, with mutations leading to skipping of exon 10 or exon 15 not encoding functional protein variants. Higher amounts of wild-type ATP7A transcript are present in occipital horn syndrome compared with Menkes disease, indicating that even a small percentage of wild-type transcript can permit the occipital horn syndrome phenotype.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Review
Medicine, General & Internal
Beata Kasztelan-Szczerbinska, Halina Cichoz-Lach
Summary: Wilson's disease is a rare autosomal recessive disorder characterized by hepatocellular copper deposition. The diagnostic approach involves a complex set of clinical findings and relies on patient history, physical examination, and laboratory testing. Timely identification of signs and symptoms using novel biomarkers and modern diagnostic tools can reduce treatment delays and improve patient prognosis. Proper management of WD includes early diagnosis, lifelong monitoring, strict adherence to treatment, and screening for adverse effects. Liver transplantation is performed in about 5% of WD patients with acute liver failure or signs of decompensation. Increasing awareness among health professionals and emphasizing early recognition of signs and symptoms are important strategies for patient safety and efficacy of WD therapy.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Immunology
Yixuan Zhou, Leiliang Zhang
Summary: This review discusses the key features and trafficking mechanisms of copper transporters ATP7A/B and examines the intricate interplay between microbes and copper metabolism. It highlights how microbes can perturb copper homeostasis through interactions with host factors.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Review
Medicine, General & Internal
Grazyna Gromadzka, Maria Bendykowska, Adam Przybylkowski
Summary: Summary: This article summarizes the methods and results of genetic research on Wilson's disease. Due to the large number of known variants in the ATP7B gene, the usefulness of genetic tests in routine diagnostics is relatively limited. Additional tests, including biochemical evidence, are needed to confirm the diagnosis of Wilson's disease. The article also highlights the complex relationships between genotype and phenotype in Wilson's disease, as other genetic and epigenetic factors also play a role.
Article
Clinical Neurology
Zi-Wei Zheng, Meng-Hui Xu, Chuan-Bin Sun, Zhi-Ying Wu, Yi Dong
Summary: This study reported a case of a patient with Wilson's disease (WD) who presented with acute-onset visual impairment. By reviewing previous cases, it was found that WD has complex clinical manifestations. Although the etiology behind visual impairment remains uncertain, the possibility of WD should be considered through neuropsychiatric and hepatic symptoms, corneal K-F rings, decreased serum ceruloplasmin, and low likelihood or exclusion of other causes. Clinicians need to recognize this rare manifestation and provide appropriate treatment to avoid misdiagnosis and overtreatment.
FRONTIERS IN NEUROLOGY
(2022)
Review
Cell Biology
Svetlana Lutsenko
Summary: Copper homeostasis is crucial for the development and function of organisms, with misbalance leading to serious pathologies. Mammalian Cu(I) transporters play a key role in regulating intracellular copper fluxes, with various regulatory proteins contributing to the dynamic and cell-specific nature of the copper transport networks. The comparison of copper transport mechanisms in the liver and intestine highlights the distinct composition and regulatory responses of their transporters to changing copper levels.
JOURNAL OF CELL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Daniela Fanni, Clara Gerosa, Valeria Marina Nurchi, Rosita Cappai, Marta Mureddu, Peter Van Eyken, Luca Saba, Mirko Manchia, Gavino Faa
Summary: Wilson's disease is a congenital disorder of copper metabolism with unknown pathogenesis. Individuals with the same genotype may exhibit different clinical presentations, potentially due to the inability to correlate mutation types in the ATP7B gene with phenotypic manifestations.
CURRENT MEDICINAL CHEMISTRY
(2021)
Review
Medicine, General & Internal
Ju Zou, Ying-Hao Wang, Ling Wang, Ruo-Chan Chen
Summary: This is a case of a 19-year-old woman with Wilson's disease, rare ATP7B gene mutation, and unusual symptoms such as photosensitivity, sensation abnormality, and skin eruption; symptoms improved after medication and plasma exchange, but she eventually underwent liver transplantation.
FRONTIERS IN MEDICINE
(2021)
Review
Endocrinology & Metabolism
S. De Feyter, A. Beyens, B. Callewaert
Summary: Counseling in ATP7A-related disorders is challenging due to clinical overlap, lack of predictive biomarkers, and genotype-phenotype correlation. A systematic literature review identified clinical criteria, evaluated genotype-phenotype correlations, and proposed management guidelines based on data from 162 individuals with confirmed ATP7A-related disorders.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Medicine, Research & Experimental
Wai-In Ho, Yang Hu, Chi-Wa Cheng, Rui Wei, Jiayin Yang, Na Li, Ka-Wing Au, Yiu-Lam Tse, Qiuyun Wang, Kwong-Man Ng, Miguel A. Esteban, Hung-Fat Tse
Summary: In this study, liposome-encapsulated curcumin (LEC) was used to treat a mouse model of Wilson's disease (WD). The treatment was found to attenuate liver injuries, restore lipid metabolism, decrease inflammation and fibrosis, and reduce hepatosplenomegaly in the mice. The mechanism of action was through the suppression of HMGB1-mediated hepatic and systemic inflammation.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Medicine, General & Internal
Anna Jopowicz, Beata Tarnacka
Summary: Wilson's disease is a rare autosomal recessive disorder caused by mutations in the ATP7B gene. It leads to copper overload in liver cells, as well as other organs like the brain, resulting in various symptoms including hepatic, neurological, and psychiatric. Treatment options include chelation therapy, zinc salts, and liver transplantation, with new medications being investigated. Early screening for Wilson's disease is important for prompt diagnosis and better treatment outcomes.
Review
Biochemistry & Molecular Biology
May T. Maung, Alyssa Carlson, Monserrat Olea-Flores, Lobna Elkhadragy, Kyle M. Schachtschneider, Napoleon Navarro-Tito, Teresita Padilla-Benavides
Summary: Copper is an essential micronutrient for human health, involved in critical metabolic reactions and signaling pathways. Maintaining copper balance and transport is crucial for proper cellular function and overall health. Copper plays a dual role in cancer, both promoting tumor growth and inducing oxidative stress in cancer cells, and is also involved in cancer treatment as a component of drugs and regulator of drug sensitivity.
Article
Cell Biology
Amika Singla, Qing Chen, Kohei Suzuki, Jie Song, Alina Fedoseienko, Melinde Wijers, Adam Lopez, Daniel D. Billadeau, Bart van de Sluis, Ezra Burstein
Summary: The study found that COMMD protein deficiency in enterocytes had minimal effects on ATP7A and did not alter copper levels under high or low copper diets, indicating that regulation of ATP7A in enterocytes may not have significant physiological consequences. However, deficiency of any of the three COMMD genes (Commd1, Commd6, or Commd9) resulted in hepatic copper accumulation under high-copper diets, likely due to destabilization of the entire CCC complex. Overall, the CCC complex plays an important role in ATP7B endosomal recycling and function.
DISEASE MODELS & MECHANISMS
(2021)