{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:48:34Z","timestamp":1790898514419,"version":"4.1.0"},"reference-count":112,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Iron is an essential micronutrient that plays a central role in numerous biological processes. Despite its relatively low abundance in the human body, iron is particularly critical for brain function. Systemic and cerebral iron homeostasis is tightly regulated through coordinated mechanisms involving absorption, transport, storage, and recycling. Within the brain, iron metabolism is further controlled by the blood\u2013brain barrier and specialized neural cell populations, including neurons, astrocytes, oligodendrocytes, and microglia. Iron is indispensable for neurodevelopment, supporting neurogenesis, myelination, and neurotransmitter synthesis. However, both iron deficiency and iron overload have detrimental consequences. Early-life iron deficiency disrupts neural development and leads to long-lasting cognitive, motor, and behavioral impairments, whereas excessive iron accumulation promotes oxidative stress, ferroptosis, and neuroinflammation. These mechanisms have been described to contribute to the pathogenesis of major neurodegenerative disorders, including Alzheimer\u2019s disease, Parkinson\u2019s disease, neurodegeneration with brain iron accumulation, and amyotrophic lateral sclerosis. This review first outlines systemic and brain iron metabolism, highlighting how neural cells regulate homeostasis. Next, it examines iron\u2019s physiological roles, particularly in neurogenesis and neurodevelopment. Finally, it explores iron\u2019s involvement in neurodegenerative diseases, emphasizing neuroinflammation as a primary mechanism of iron toxicity.<\/jats:p>","DOI":"10.3390\/cells15110999","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:37:29Z","timestamp":1780544249000},"page":"999","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Iron in Neuronal Homeostasis: A Double-Edged Sword"],"prefix":"10.3390","volume":"15","author":[{"given":"Bibiana","family":"Sgalletta","sequence":"first","affiliation":[{"name":"Department of Biology, University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Agostini","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3968-8418","authenticated-orcid":false,"given":"Marco","family":"Bisaglia","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, Via Ugo Bassi 58\/B, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10534-022-00380-x","article-title":"Relevance of Biometals during Neuronal Differentiation and Myelination: In Vitro and In Vivo Studies","volume":"35","author":"Montes","year":"2022","journal-title":"Biometals"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(04)00343-5","article-title":"Balancing Acts: Molecular Control of Mammalian Iron Metabolism","volume":"117","author":"Hentze","year":"2004","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Shi, Y., Sun, M., and Wang, B. 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