{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:57:22Z","timestamp":1793505442716,"version":"4.5.0"},"reference-count":153,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Stress is a non-specific systemic response to internal or external challenges. Recent studies show that stress can disrupt iron metabolism and that iron dyshomeostasis is implicated in many diseases-particularly within the nervous system, where iron distribution and regulation intersect tightly with oxidative stress and inflammation. Activation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis by stress can upregulate hepatic hepcidin and reprogram systemic iron fluxes, leading to functional iron deficiency and, in the brain, reduced iron availability, which affects myelination and neurotransmitter metabolism. Conversely, iron dyshomeostasis also contributes to neurodegenerative pathology. In this review, we synthesize recent evidence of how stress reprograms brain iron distribution and regulation, and we outline the mechanistic links between stress-induced iron dysregulation and neurological pathology. We also discuss the therapeutic implications (such as iron-chelation strategies) and highlight the three-way interplay among stress, iron metabolism, and neurodegeneration. These insights suggest that managing iron homeostasis may offer new therapeutic avenues for stress-related neural disorders.<\/jats:p>","DOI":"10.3390\/biology14111575","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T10:56:27Z","timestamp":1762858587000},"page":"1575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Stress-Induced Dysregulation of Brain Iron Metabolism and Its Links to Neurological Disorders"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3953-3594","authenticated-orcid":false,"given":"Ke","family":"Dong","sequence":"first","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing 100850, China"},{"name":"Department of Neurosurgery, First Medical Center of the PLA General Hospital, Beijing 100853, China"},{"name":"School of Medicine, South China University of Technology, Guangzhou 511442, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Medical Center of the PLA General Hospital, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xie","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, First Medical Center of the PLA General Hospital, Beijing 100853, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjia","family":"Qian","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3823","DOI":"10.1182\/blood.V98.13.3823","article-title":"Characterization of the iron transporter DMT1 (NRAMP2\/DCT1) in red blood cells of normal and anemic mk\/mk mice","volume":"98","author":"Zhang","year":"2001","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1182\/blood-2002-04-1182","article-title":"Iron transporter Nramp2\/DMT-1 is associated with the membrane of phagosomes in macrophages and Sertoli cells","volume":"100","author":"Jabado","year":"2002","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00109-015-1362-3","article-title":"miR-20a regulates expression of the iron exporter ferroportin in lung cancer","volume":"94","author":"Babu","year":"2016","journal-title":"J. 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