{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:28:51Z","timestamp":1790281731634,"version":"4.1.0"},"reference-count":187,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metallothioneins (MTs) are small molecular\u2010weight proteins that either bind or release essential transition metals, depending on a specific cell situation. There are 4 major isoforms of MTs (1\u20134), of which MT1\/2 is found in every cell in the body.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To provide a comprehensive discussion on the role of metallothionein in human pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review was conducted using a variety of search engines, including Google Scholar, PubMed Central, Scopus, Web of Science, and others.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The antioxidant property of MT is enhanced based on the availability of zinc. MTs reduce Pro\u2010inflammatory cytokine production and shift the Th17\/Treg balance, ultimately alleviating inflammatory diseases. In neurodegenerative diseases, MTs interact with protein aggregates and modulate their formation and toxicity. The MT's molecular processes in neurodegenerative illnesses include metal ion control, antioxidant activity, and anti\u2010inflammatory actions. In cancer, MT acts as a tumor suppressor in the early stages and promotes tumor progression in the later stages. Only a few MT isoform\u2010targeting approaches have been approved for use as therapeutic drugs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metallothioneins play vital roles in controlling oxidative stress, immunity, metal homeostasis and protein aggregate for many diseases. Their dual roles as defenders in inflammation and neurodegeneration, and as suppressors and facilitators in cancer, highlight the complex nature of their biological role.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.71279","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T03:31:40Z","timestamp":1758598300000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Emerging Roles of Metallothioneins in Human Pathophysiology: A Review"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-2827","authenticated-orcid":false,"given":"Ousman","family":"Mohammed","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia"},{"name":"Department of Medical Laboratory Sciences, College of Medicine and Health Sciences Wollo University Dessie Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdisa","family":"Tufa","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5281-8611","authenticated-orcid":false,"given":"Solomon Tebeje","family":"Gizaw","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Medicine, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01574a064"},{"issue":"9","key":"e_1_2_12_3_1","first-page":"638","article-title":"Role of Metallothionein to Moderate Heavy Metals Toxicity in Animals: A Review","volume":"8","author":"Bhardwaj H.","year":"2021","journal-title":"Cancer"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.2478\/aiht-2020-71-3349"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-009-9586-3"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13184530"},{"issue":"1","key":"e_1_2_12_7_1","first-page":"57","article-title":"Metal\u2010Binding Protein: Metallothionein","volume":"6","author":"Marikar F.","year":"2023","journal-title":"International Journal of Medical Biochemistry"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100691"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13070825"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5828056"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102197"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmrp.2017.02.006"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-017-1119-7"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.006281"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7CS00448F"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041619198"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2023.2173078"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12030360"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2020.100691"},{"key":"e_1_2_12_20_1","first-page":"347","article-title":"Nuclear Localization of Metallothionein During Cell Proliferation and Differentiation","volume":"46","author":"Cherian M. 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