{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:11:47Z","timestamp":1790813507314,"version":"4.1.0"},"reference-count":190,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Wilson\u2019s disease (WD) is inherited in an autosomal recessive manner and is caused by pathogenic variants of the ATP7B gene, which are responsible for impaired copper transport in the cell, inhibition of copper binding to apoceruloplasmin, and biliary excretion. This leads to the accumulation of copper in the tissues. Copper accumulation in the CNS leads to the neurological and psychiatric symptoms of WD. Abnormalities of copper metabolism in WD are associated with impaired iron metabolism. Both of these elements are redox active and may contribute to neuropathology. It has long been assumed that among parenchymal cells, astrocytes have the greatest impact on copper and iron homeostasis in the brain. Capillary endothelial cells are separated from the neuropil by astrocyte terminal legs, putting astrocytes in an ideal position to regulate the transport of iron and copper to other brain cells and protect them if metals breach the blood\u2013brain barrier. Astrocytes are responsible for, among other things, maintaining extracellular ion homeostasis, modulating synaptic transmission and plasticity, obtaining metabolites, and protecting the brain against oxidative stress and toxins. However, excess copper and\/or iron causes an increase in the number of astrocytes and their morphological changes observed in neuropathological studies, as well as a loss of the copper\/iron storage function leading to macromolecule peroxidation and neuronal loss through apoptosis, autophagy, or cuproptosis\/ferroptosis. The molecular mechanisms explaining the possible role of glia in copper- and iron-induced neurodegeneration in WD are largely understood from studies of neuropathology in Parkinson\u2019s disease and Alzheimer\u2019s disease. Understanding the mechanisms of glial involvement in neuroprotection\/neurotoxicity is important for explaining the pathomechanisms of neuronal death in WD and, in the future, perhaps for developing more effective diagnostic\/treatment methods.<\/jats:p>","DOI":"10.3390\/ijms25147545","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T09:23:08Z","timestamp":1720603388000},"page":"7545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Role of Glia in Wilson\u2019s Disease: Clinical, Neuroimaging, Neuropathological and Molecular Perspectives"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-8971","authenticated-orcid":false,"given":"Gra\u017cyna","family":"Gromadzka","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University, W\u00f3ycickiego 1\/3, 01-938 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-5168","authenticated-orcid":false,"given":"Anna","family":"Wilkaniec","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawi\u0144skiego St., 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9902-5969","authenticated-orcid":false,"given":"Beata","family":"Tarnacka","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Medical University of Warsaw, Sparta\u0144ska 1, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0471-3350","authenticated-orcid":false,"given":"Krzysztof","family":"Hadrian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4900-9549","authenticated-orcid":false,"given":"Maria","family":"Bendykowska","sequence":"additional","affiliation":[{"name":"Students Scientific Association \u201cImmunis\u201d, Cardinal Stefan Wyszynski University, Dewajtis 5, 01-815 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5851-2856","authenticated-orcid":false,"given":"Adam","family":"Przyby\u0142kowski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-9651","authenticated-orcid":false,"given":"Tomasz","family":"Litwin","sequence":"additional","affiliation":[{"name":"Second Department of Neurology, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/mds.20694","article-title":"History of Wilson\u2019s disease: 1912 to 2000","volume":"21","author":"Walshe","year":"2006","journal-title":"Mov. 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