{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:51Z","timestamp":1788415971754,"version":"build-2803163510"},"reference-count":218,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Oxidative stress, iron dyshomeostasis, and chronic neuroinflammation are the principal mechanisms involved in the progression of central nervous system (CNS) disorders, which are a significant source of death and chronic disability worldwide. This review focuses on understanding the mechanistic relationship between ferroptosis and neuroinflammation in central nervous system (CNS) disorders, which involves the molecular mechanisms, their role in the pathogenesis of the disease, and therapeutic opportunities available. Ferroptosis is a regulated form of cell death triggered by iron-catalyzed lipid peroxidation, glutathione depletion and inactivation of glutathione peroxidase 4 (GPX4), resulting in neuronal injury. The increased generation of ROS in the cell due to the presence of excess iron catalyzes Fenton chemistry, which leads to lipid peroxidation of the cell membrane and ferroptotic cell death, and damage-associated molecular patterns originating from the ferroptotic cell death promote the activation of NF-\u03baB-dependent inflammatory signaling pathways and inflammasome formation. Excessive dysregulations involving the hepcidin-ferroportin axis, DMT1\u2013transferrin transport, ferritin\u2013NCOA4-mediated ferritinophagy, and regulatory pathways like Nrf2, IRP\/IRE, and SIRT1 intensify oxidative stress, ferroptosis and neuroinflammation in neurodegenerative and acute CNS disorders. The role of several key molecular mediators such as SIRT1, Nrf2, NF-\u03baB, iNOS\/NO\u25cf, and COX-2 in connecting ferroptotic and inflammatory signaling pathways is also discussed in this review. This understanding of the mechanism of these players gives a mechanistic framework for the development of targeted therapeutic and nutritional interventions to reduce neuronal damage and help slow the progression of CNS disorders.<\/jats:p>","DOI":"10.3389\/fnagi.2026.1874307","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:16:55Z","timestamp":1788412615000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ferroptosis\u2013neuroinflammation interplay: mechanistic pathways and therapeutic opportunities in central nervous system disorders"],"prefix":"10.3389","volume":"18","author":[{"given":"Khuzin","family":"Dinislam","sequence":"first","affiliation":[{"name":"Department of General Chemistry, Bashkir State Medical University, Republic of Bashkortostan","place":["Ufa, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriy A.","family":"Kataev","sequence":"additional","affiliation":[{"name":"Bashkir State Medical University, Ministry of Health of the Russian Federation","place":["Ufa, Russia"]},{"name":"Ufa University of Science and Technology","place":["Ufa, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Rehan Ajmal","sequence":"additional","affiliation":[{"name":"Physical Biochemistry Research Laboratory, Department of Biochemistry, Faculty of Science, University of Tabuk","place":["Tabuk, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman S.","family":"Amer","sequence":"additional","affiliation":[{"name":"Department of Basic Medical and Dental Sciences, College of Dentistry, Ajman University","place":["Ajman, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratibha","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Basic Medical and Dental Sciences, College of Dentistry, Ajman University","place":["Ajman, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azna","family":"Zuberi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Northwestern University","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1134\/S0003683820060022","article-title":"Peroxynitrite: Toxic agent and signaling molecule.","volume":"56","author":"Abalenikhina","year":"2020","journal-title":"Appl. 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