{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:28:00Z","timestamp":1772252880992,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009873","name":"Regione Autonoma della Sardegna","doi-asserted-by":"publisher","award":["RASSR79857"],"award-info":[{"award-number":["RASSR79857"]}],"id":[{"id":"10.13039\/501100009873","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thymosin \u03b24 (T\u03b24) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. T\u03b24 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of T\u03b24 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of T\u03b24 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of T\u03b24 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, T\u03b24 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that T\u03b24 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of T\u03b24 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled T\u03b24 release could command on\/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.<\/jats:p>","DOI":"10.3390\/ijms23010551","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Thymosin \u03b24 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4644-761X","authenticated-orcid":false,"given":"Joanna I.","family":"Lachowicz","sequence":"first","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giusi","family":"Pichiri","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Piludu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Fais","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, OBL Oral Biotechnology Laboratory, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germano","family":"Orr\u00f9","sequence":"additional","affiliation":[{"name":"Department of Surgical Science, OBL Oral Biotechnology Laboratory, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terenzio","family":"Congiu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0189-8612","authenticated-orcid":false,"given":"Gavino","family":"Faa","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Fanni","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9652-9659","authenticated-orcid":false,"given":"Gabriele","family":"Dalla Torre","sequence":"additional","affiliation":[{"name":"Kimika Fakultatea, Euskal Herriko Unibertsitatea UPV\/EHU, Donostia International Physics Center (DIPC), P.K. 1072 Donostia Euskadi, 20080 San Sebastian, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xabier","family":"Lopez","sequence":"additional","affiliation":[{"name":"Kimika Fakultatea, Euskal Herriko Unibertsitatea UPV\/EHU, Donostia International Physics Center (DIPC), P.K. 1072 Donostia Euskadi, 20080 San Sebastian, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kousik","family":"Chandra","sequence":"additional","affiliation":[{"name":"Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kacper","family":"Szczepski","sequence":"additional","affiliation":[{"name":"Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7684-9359","authenticated-orcid":false,"given":"Lukasz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitra","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul-Hamid","family":"Emwas","sequence":"additional","affiliation":[{"name":"Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Castagnola","sequence":"additional","affiliation":[{"name":"Institute of Chemistry of Molecular Recognition, National Research Council (Consiglio Nazionale delle Ricerche), 00185 Rome, Italy"},{"name":"Laboratory of Proteomics and Metabolomics, IRCCS, Santa Lucia Foundation, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariusz","family":"Jaremko","sequence":"additional","affiliation":[{"name":"Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3443-980X","authenticated-orcid":false,"given":"Ewald","family":"Hannappel","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nuremberg, 91058 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierpaolo","family":"Coni","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/imr.12533","article-title":"Ferroptosis: Bug or feature?","volume":"277","author":"Dixon","year":"2017","journal-title":"Immunol. 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