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
Ana Lucena-Valera, Pilar Ruz-Zafra, Javier Ampuero
Summary: Wilson's disease is a rare hereditary disorder caused by a deficiency in the ATP7B transporter. It results in copper accumulation primarily in the liver, and secondarily in other organs such as the central nervous system. The disease has a wide spectrum of symptoms, ranging from asymptomatic to acute liver failure. Diagnosis requires a combination of clinical signs, symptoms, and diagnostic tests. Treatment involves lifelong maintenance with chelating agents and copper absorption inhibitors, and liver transplant may be an option for end-stage liver disease patients.
Article
Clinical Neurology
Jasodhara Chaudhuri, Samar Biswas, Goutam Gangopadhyay, Tamoghna Biswas, Jyotishka Datta, Atanu Biswas, Alak Pandit, Amlan Kusum Datta, Adreesh Mukherjee, Atanu Kumar Dutta, Paramita Bhattacharya, Avijit Hazra
Summary: The study aimed to correlate genotype with clinical and radiological features in Indian WD patients. The most important features for predicting common mutation were revealed by statistical methods, but further studies are needed for a better understanding of the genetic landscape of Wilson disease.
ACTA NEUROLOGICA BELGICA
(2022)
Review
Medicine, General & Internal
Grazyna Gromadzka, Marta Grycan, Adam M. Przybylkowski
Summary: Wilson's disease (WND) is a genetic disorder affecting copper metabolism. Multiple diagnostic tools are available to diagnose and monitor WND. Laboratory tests for copper metabolism disorders play a significant role in diagnosis.
Review
Cell Biology
Som Dev, Robert L. Kruse, James P. Hamilton, Svetlana Lutsenko
Summary: This review summarizes recent advances in the characterization of Wilson disease pathophysiology and discusses emerging targets for improving diagnosis and treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Abigael Muchenditsi, C. Conover Talbot, Aline Gottlieb, Haojun Yang, Byunghak Kang, Tatiana Boronina, Robert Cole, Li Wang, Som Dev, James P. Hamilton, Svetlana Lutsenko
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
Saleh A. Alqahtani, Rose Chami, Dua Abuquteish, Shannon M. Vandriel, Charesse Yap, Liyana Kukkadi, Aishwarya Parmar, Amrita Mundh, Eve A. Roberts, Binita M. Kamath, Iram Siddiqui
Summary: This study compared the histological features of Wilson disease (WD) in children with non-alcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH). It found that there was considerable overlap in the light microscopic findings, but ultrastructural findings of mitochondrial abnormalities were important in distinguishing WD from NAFLD and AIH.
LIVER INTERNATIONAL
(2022)
Article
Gastroenterology & Hepatology
Mingming Li, Jing Ma, Wenlong Wang, Xu Yang, Kaizhong Luo
Summary: In this study, three novel mutations were identified in 103 WD patients from southern China, enriching the mutational spectrum of the ATP7B gene. The most common mutations were c.2333G>T (p.Arg778 Leu) and c.2975C>T (p.Pro992Leu), with allelic frequencies of 28.6% and 13.0%, respectively. Phenotype-genotype correlation analysis revealed significant associations between certain mutations and clinical characteristics of WD, providing insights into the population genetics of WD in China.
BMC GASTROENTEROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Bryce Blades, Scott Ayton, Ya Hui Hung, Ashley Bush, Sharon La Fontaine
Summary: The complex and inverse relationship between copper and lipid metabolism has implications for diseases involving dyslipidemia. Understanding these pathways may provide druggable targets for therapeutic intervention. Tissue-specific roles of the copper regulatory protein ATP7B further elucidate the association between copper and lipid metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Pediatrics
Aabha Nagral, Snehal Mallakmir, Nikita Garg, Kritika Tiwari, Suzena Masih, Nishtha Nagral, Ojas Unavane, Ajay Jhaveri, Shubha Phadke, GaneshPrasad ArunKumar, Rakesh Aggarwal
Summary: This study reports genotype data of Wilson disease patients from India, adding to the available spectrum of causative variants in ATP7B gene. It also found genetic and phenotypic diversity in the Indian population.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Genetics & Heredity
Lihua Wu, Jianhong Wang, Lei Wang, Qi Xu, Bo Zhou, Zhen Zhang, Qi Li, Hui Wang, Lu Han, Qian Jiang, Lin Wang
Summary: This study provides detailed knowledge about the clinical manifestations, genetic spectrum, and physical, language, neurodevelopment features and genotype-phenotype correlations of Chinese patients with Mowat-Wilson syndrome (MWS). The study found that all patients had lower height and weight, and some had microcephaly. Patients performed better in cognitive play and social communication than in receptive and expressive language.
FRONTIERS IN GENETICS
(2022)
Article
Gastroenterology & Hepatology
Gaurav V. Sarode, Tagreed A. Mazi, Kari Neier, Noreene M. Shibata, Guillaume Jospin, Nathaniel H. O. Harder, Amanda Caceres, Marie C. Heffern, Ashok K. Sharma, Shyam K. More, Maneesh Dave, Shannon M. Schroeder, Li Wang, Janine M. Lasalle, Svetlana Lutsenko, Valentina Medici
Summary: This study investigates the role of gut microbiota and lipidome in Wilson disease (WD). The results show reduced gut microbiota diversity and dysregulated lipid metabolism in animal models of WD. Interestingly, the deficiency of ATP7B in the intestine affects the systemic response to a high-fat challenge but does not influence the gut microbiome profile.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Dermatology
Weilong Zhong, Linghan Hu, Xu Cao, Jiahui Zhao, Xianning Zhang, Mingyang Lee, Huijun Wang, Jie Zhang, Quan Chen, Cheng Feng, Lina Duo, Xiuli Wang, Li Tang, Zhimiao Lin, Yong Yang
Summary: The study identified new and recurrent variations in the TRPV3 gene in patients with Olmsted syndrome, finding that variations in specific regions of the gene significantly enhance channel function and lead to severe phenotypes, while other variations have milder effects.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
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
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)
Article
Chemistry, Inorganic & Nuclear
Kallol Purkait, Ruturaj, Arindam Mukherjee, Arnab Gupta
INORGANIC CHEMISTRY
(2019)
Article
Chemistry, Inorganic & Nuclear
Moumita Maji, Sourav Acharya, Saptarshi Maji, Kallol Purkait, Arnab Gupta, Arindam Mukherjee
INORGANIC CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Taniya Mandal, Sumanta Kar, Saptarshi Maji, Samarpita Sen, Arnab Gupta
JOURNAL OF MEMBRANE BIOLOGY
(2020)
Article
Cell Biology
Santanu Das, Saptarshi Maji, Ruturaj, Indira Bhattacharya, Tanusree Saha, Nabanita Naskar, Arnab Gupta
JOURNAL OF CELL SCIENCE
(2020)
Article
Biochemistry & Molecular Biology
Rupam Paul, Sourav Banerjee, Samarpita Sen, Pratiksha Dubey, Saptarshi Maji, Anand K. Bachhawat, Rupak Datta, Arnab Gupta
Summary: Copper is essential for life, but excessive amounts can be toxic. Leishmania parasites have high tolerance to copper stress and employ LmATP7 to survive in host macrophages. The interaction between Leishmania and macrophages involves upregulation of host ATP7A and increased expression of LmATP7. Overexpression of LmATP7 enhances parasite survivability within macrophages.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Sumanta Kar, Samarpita Sen, Saptarshi Maji, Deepashri Saraf, Ruturaj, Rupam Paul, Sohini Dutt, Basudeb Mondal, Enrique Rodriguez-Boulan, Ryan Schreiner, Durba Sengupta, Arnab Gupta
Summary: The extracellular amino-terminus of human CTR1 contains two methionine-histidine clusters and neighboring aspartates that bind Cu(I) and Cu(II) and play a crucial role in copper uptake and endocytosis. The reduction of Cu(II) to Cu(I) and subsequent coordination by the methionine cluster are important for regulating the localization and internalization of CTR1. This study provides new insights into the mechanisms of copper bioutilization.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Materials Science, Biomaterials
Basudeb Mondal, Abinash Padhy, Saptarshi Maji, Arnab Gupta, Sayam Sen Gupta
Summary: Stimuli-responsive cross-linked nanocarriers that induce lysosomal cell death have been synthesized and attracted the attention of researchers in the biomedical field. These nanocarriers have advantages such as remaining intact during blood circulation and reaching the target site via receptor-mediated endocytosis, enhancing therapeutic efficacy and reducing side effects.
BIOMATERIALS SCIENCE
(2023)
Article
Cell Biology
Saptarshi Maji, Marinella Pirozzi, Raviranjan Ruturaj, Raviranjan Pandey, Tamal Ghosh, Santanu Das, Arnab Gupta
Summary: In hepatocytes, the ATP7B protein is located on the trans-Golgi network and transports excess copper out of the cell through lysosomal exocytosis. Our study reveals that ATP7B can be found in the endolysosomal compartment of hepatocytes even in the absence of copper or after copper chelation. These ATP7B-containing lysosomes are in close proximity to the TGN. ATP7B is distributed between the acidic sub-domain of the TGN and the TGN-proximal lysosomes. We also discovered that ATP7B is recycled to the TGN-proximal lysosomes instead of returning to the TGN after copper chelation, suggesting the importance of these lysosomes in the retrograde pathway of ATP7B.
Article
Chemistry, Inorganic & Nuclear
Moumita Maji, Subhendu Karmakar, Ruturaj, Arnab Gupta, Arindam Mukherjee
DALTON TRANSACTIONS
(2020)