{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:04:21Z","timestamp":1792145061522,"version":"4.4.0"},"reference-count":231,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["PNRR M4C2-Investimento 1.4-CN00000041"],"award-info":[{"award-number":["PNRR M4C2-Investimento 1.4-CN00000041"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Ferroptosis is a novel iron-sensitive subtype of regulated cell death (RCD), persisting under extreme lipid peroxidation and iron\/redox imbalances. Unlike apoptosis, necroptosis, and pyroptosis, ferroptosis is a signaling-driven process mediated through iron metabolism imbalance, polyunsaturated fatty acid (PUFA) exceeding oxidation, and defects in its protective systems like Xc-\/GSH\/GPx4. Specifically, this review establishes that iron-driven ferroptosis is a central underlying pathomechanistic factor in a broad range of human diseases. Significantly, whether its modulation is therapeutic, it is entirely conditional on the specific disease context. Thus, its induction can provide a promising antidote for destructive cancer cells when conjoined with immuno-therapies to boost anticancer immunity. Conversely, iron-mediated ferroptosis suppression is a key factor in countering destructive changes in a whole range of degenerative and acute injuries. Current therapeutic approaches include iron chelators, lipid oxidation inhibitors, GPx4 activators, natural and active compounds, and novel drug delivery systems. However, against all odds and despite its intense therapeutic promise, its translation into a practical medicinal strategy faces many difficulties. Thus, a therapeutic agent specifically focused on its modulation is still lacking. The availability of selective biologic markers is a concern. The challenges in the direct pathologic identification of ferroptosis in a complex in vivo systemic scenario remain. Current avenues for its future development are pathogen infections, the discovery of novel regulating factors, and novel approaches to personalized medicine centered on its organ-level in vivo signatures.<\/jats:p>","DOI":"10.3390\/antiox14121411","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"1411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-449X","authenticated-orcid":false,"given":"Ilaria","family":"Artusi","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine (DMM), University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"},{"name":"Department of Pharmaceuticals and Pharmacological Sciences (DSF), University of Padua, Via Marzolo 5, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9875-9706","authenticated-orcid":false,"given":"Michela","family":"Rubin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine (DMM), University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4367-6093","authenticated-orcid":false,"given":"Giovanni","family":"Cravin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine (DMM), University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5155-4682","authenticated-orcid":false,"given":"Giorgio","family":"Cozza","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine (DMM), University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"},{"name":"Biostructures and Biosystems National Institute (INBB), Via dei Carpegna 19, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.cell.2011.10.033","article-title":"Programmed Cell Death in Animal Development and Disease","volume":"147","author":"Fuchs","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/bjc.1972.33","article-title":"Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics","volume":"26","author":"Kerr","year":"1972","journal-title":"Br. 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