{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:34:13Z","timestamp":1781015653063,"version":"3.54.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS112642"],"award-info":[{"award-number":["R01NS112642"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neuroinflammatory conditions linked to iron dysregulation pose significant challenges in neurodegenerative diseases. Iron\u2010loaded microglia are observed in the brains of patients with various neuroinflammatory conditions, yet how iron overload affects microglial function and contributes to various neuroinflammatory processes is poorly understood. This in\u00a0vitro study elucidates the relationship between excess iron, cofilin activation, and microglial function, shedding light on potential therapeutic avenues. Iron overload was induced in Human Microglial Clone 3 cells using ferrous sulfate, and the expressions of ferritin heavy chain, ferritin light chain, divalent metal transporter 1, cofilin, p\u2010cofilin, nuclear factor\u2010\u03baB (NF\u2010\u03baB), and various inflammatory cytokines were analyzed using real\u2010time quantitative polymerase chain reaction, immunocytochemistry, Western blotting, and enzyme\u2010linked immunosorbent assay. Results revealed a notable increase in cofilin, NF\u2010\u03baB, and inflammatory cytokine expression levels following excess iron exposure. Moreover, treatment with deferoxamine (DFX), a known iron chelator, and a novel cofilin inhibitor (CI) synthesized in our laboratory demonstrate a mitigating effect on iron\u2010induced cofilin expression. Furthermore, both DFX and CI exhibit promising outcomes in mitigating the inflammatory consequences of excess iron, including the expression of pro\u2010inflammatory cytokines and NF\u2010\u03baB activation. These findings suggest that both DFX and CI can potentially alleviate microglia\u2010induced neuroinflammation by targeting both iron dysregulation and cofilin\u2010mediated pathways. Overall, this study provides valuable insights into iron\u2010induced cofilin activation and microglial activation, offering avenues for potential targeted therapies for neuroinflammatory conditions associated with iron and cofilin dysregulation in neurodegenerative diseases.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16260-fig-0010-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16260","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T12:19:06Z","timestamp":1731932346000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of iron\u2010induced cofilin activation and inflammation in microglia by a novel cofilin inhibitor"],"prefix":"10.1111","volume":"169","author":[{"given":"Faheem","family":"Shehjar","sequence":"first","affiliation":[{"name":"Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonisamy William","family":"James","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reetika","family":"Mahajan","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-1618","authenticated-orcid":false,"given":"Zahoor A.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicinal and Biological Chemistry College of Pharmacy and Pharmaceutical Sciences  Toledo Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.2c00010"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-015-0438-2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-017-0432-7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.040871"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.274330"},{"key":"e_1_2_11_7_1","volume-title":"Neuroinflammation and cognitive deficits in aging: Possible role of cofilin signaling","author":"Alsegiani A. 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