{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:24:51Z","timestamp":1781825091163,"version":"3.54.5"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007950","name":"Tanta University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007950","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurochem Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Multiple sclerosis (MS) is a progressive, immune-mediated demyelinating disorder of the central nervous system (CNS). Kaempferol (KAM), a dietary bioflavonoid found in many edible and medicinal plants, exhibits significant neuroprotective effects in various immunological and neurological disorders; however, its therapeutic potential in MS remains largely unexplored. This study aimed to investigate the protective effects of KAM and the underlying molecular mechanisms using an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. 40 female C57B1\/6 mice were assigned to 4 groups: Normal control [saline (i.d.)\u2009+\u2009DMSO (i.p.)]; KAM [saline (i.d.)\u2009+\u2009KAM (50\u00a0mg\/kg\/d, i.p.)]; EAE [MOG\n                    <jats:sup>35\u201355<\/jats:sup>\n                    immunization (i.d.)\u2009+\u2009DMSO (i.p.)]; and EAE\u2009+\u2009KAM [MOG\n                    <jats:sup>35\u201355<\/jats:sup>\n                    immunization (i.d.)\u2009+\u2009KAM (50\u00a0mg\/kg\/d, i.p.)]. The brain and spinal cord were dissected for biochemical, molecular, histopathological, electron microscopic, and immunohistochemical analysis. KAM administration efficiently reduced clinical scores and ameliorated neural cytomorphological abnormalities. KAM profoundly combated iron overload and effectively upregulated ferroportin1 (Fpn1)-encoding gene expression. Furthermore, KAM valuably counteracted neuronal ferroptosis chiefly by restoring the Slc7A11\/GSH\/GPX4 axis. KAM considerably attenuated proinflammatory cytokine IL-17 and chemokine CCL-19. Intriguingly, KAM promoted axonal remyelination as indicated by an observable escalation in myelin basic protein content through activating the cAMP\/CREB\/ciliary neurotrophic factor (CNTF) axis. Collectively, for the first time, these findings demonstrated KAM\u2019s neuroprotective potency against EAE, considering its antioxidant, anti-ferroptotic, immunomodulatory, anti-inflammatory, and neurotrophic properties, primarily mediated by inhibiting Fpn1-mediated ferroptosis, activating the cAMP\/CREB\/CNTF axis, and enhancing\n                    <jats:italic>miRNA-367-3p<\/jats:italic>\n                    expression. Accordingly, miRNA-367-3p has been proposed as an upcoming therapeutic target for MS, and KAM could be a promising treatment option for MS patients.\n                  <\/jats:p>","DOI":"10.1007\/s11064-025-04641-2","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:21:00Z","timestamp":1768389660000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Modulating miRNA-367-3p Expression by Kaempferol Alleviates Experimental Autoimmune Encephalomyelitis: Targeting Fpn1-Dependent Ferroptosis and cAMP\/CREB\/CNTF Signaling"],"prefix":"10.1007","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6106-3051","authenticated-orcid":false,"given":"Rehab M.","family":"El-Gohary","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1093-4897","authenticated-orcid":false,"given":"Heba M.","family":"Shoeib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramez A. E.","family":"Barhoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-1096","authenticated-orcid":false,"given":"Shimaa M.","family":"Badr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaimaa Mohammed","family":"Zaher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2335-3699","authenticated-orcid":false,"given":"Rehab E. Abo","family":"El Gheit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola A.","family":"Elshora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona H.","family":"Elamly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa Rizk","family":"Magar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamaleldien Elsayed","family":"Abdelkader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5792-160X","authenticated-orcid":false,"given":"Asmaa S.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"4641_CR1","doi-asserted-by":"publisher","first-page":"123402","DOI":"10.1016\/j.lfs.2025.123402","volume":"363","author":"H Qu","year":"2025","unstructured":"Qu H, Fu XX, Han S (2025) C16 peptide and angiopoietin-1 alleviate the side effects of glucocorticoids in a rat multiple sclerosis model. Life Sci 363:123402. https:\/\/doi.org\/10.1016\/j.lfs.2025.123402","journal-title":"Life Sci"},{"issue":"8","key":"4641_CR2","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.3390\/genes13081324","volume":"13","author":"S Upadhayay","year":"2022","unstructured":"Upadhayay S, Mehan S, Prajapati A et al (2022) Nrf2\/HO-1 signaling stimulation through Acetyl-11-Keto-Beta-Boswellic acid (AKBA) provides neuroprotection in ethidium bromide-induced experimental model of multiple sclerosis. Genes (Basel) 13(8):1324. https:\/\/doi.org\/10.3390\/genes13081324","journal-title":"Genes (Basel)"},{"issue":"4","key":"4641_CR3","doi-asserted-by":"publisher","first-page":"100051","DOI":"10.1016\/j.phyplu.2021.100051","volume":"1","author":"N Sharma","year":"2021","unstructured":"Sharma N et al (2021) Neuroprotection by Solanesol against ethidium bromide-induced multiple sclerosis-like neurobehavioral, molecular, and neurochemical alterations in experimental rats. Phytomed Plus 1(4):100051","journal-title":"Phytomed Plus"},{"key":"4641_CR4","doi-asserted-by":"publisher","first-page":"100019","DOI":"10.1016\/j.dscb.2021.100019","volume":"3","author":"S Upadhayay","year":"2021","unstructured":"Upadhayay S, Mehan S (2021) Targeting Nrf2\/HO-1 anti-oxidant signaling pathway in the progression of multiple sclerosis and influences on neurological dysfunctions. Brain Dis 3:100019","journal-title":"Brain Dis"},{"issue":"1","key":"4641_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1002\/eji.202149589","volume":"52","author":"L Ryan","year":"2022","unstructured":"Ryan L, Mills KHG (2022) Sex differences regulate immune responses in experimental autoimmune encephalomyelitis and multiple sclerosis. Eur J Immunol 52(1):24\u201333. https:\/\/doi.org\/10.1002\/eji.202149589","journal-title":"Eur J Immunol"},{"issue":"4","key":"4641_CR6","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.3390\/ijms25042255","volume":"25","author":"GL Cipriano","year":"2024","unstructured":"Cipriano GL, Schepici G, Mazzon E, Anchesi I (2024) Multiple sclerosis: roles of miRNA, lcnRNA, and circrna and their implications in cellular pathways. Int J Mol Sci 25(4):2255. https:\/\/doi.org\/10.3390\/ijms25042255","journal-title":"Int J Mol Sci"},{"key":"4641_CR7","doi-asserted-by":"publisher","first-page":"577995","DOI":"10.1016\/j.jneuroim.2022.577995","volume":"373","author":"X Li","year":"2022","unstructured":"Li X, Chu Y, Ma R et al (2022) Ferroptosis as a mechanism of oligodendrocyte loss and demyelination in experimental autoimmune encephalomyelitis. J Neuroimmunol 373:577995","journal-title":"J Neuroimmunol"},{"issue":"4","key":"4641_CR8","doi-asserted-by":"publisher","first-page":"493","DOI":"10.3390\/antiox13040493","volume":"13","author":"RM El-Gohary","year":"2024","unstructured":"El-Gohary RM, Okasha AH, Abd El-Azeem AH et al (2024) Uncovering the cardioprotective potential of diacerein in doxorubicin cardiotoxicity: mitigating Ferritinophagy-Mediated ferroptosis via upregulating NRF2\/SLC7A11\/GPX4 axis. Antioxid (Basel) 13(4):493. https:\/\/doi.org\/10.3390\/antiox13040493","journal-title":"Antioxid (Basel)"},{"key":"4641_CR9","doi-asserted-by":"publisher","first-page":"103463","DOI":"10.1016\/j.redox.2024.103463","volume":"79","author":"V Saverio","year":"2025","unstructured":"Saverio V, Ferrario E, Monzani R et al (2025) AKRs confer oligodendrocytes resistance to differentiation-stimulated ferroptosis. Redox Biol 79:103463. https:\/\/doi.org\/10.1016\/j.redox.2024.103463","journal-title":"Redox Biol"},{"issue":"1","key":"4641_CR10","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s42003-025-07799-1","volume":"8","author":"I Happacher","year":"2025","unstructured":"Happacher I, Oberegger S, Abt B et al (2025) FpnA, the Aspergillus fumigatus homolog of human ferroportin, mediates resistance to nickel, Cobalt and gallium but does not function in iron homeostasis. Commun Biol 8(1):399. https:\/\/doi.org\/10.1038\/s42003-025-07799-1","journal-title":"Commun Biol"},{"key":"4641_CR11","doi-asserted-by":"publisher","first-page":"101961","DOI":"10.1016\/j.arr.2023.101961","volume":"88","author":"ZM Qian","year":"2023","unstructured":"Qian ZM, Li W, Guo Q (2023) Ferroportin1 in the brain. Ageing Res Rev 88:101961. https:\/\/doi.org\/10.1016\/j.arr.2023.101961","journal-title":"Ageing Res Rev"},{"key":"4641_CR12","doi-asserted-by":"publisher","unstructured":"Bao WD, Pang P, Zhou XT et al (2024) Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer\u2019s disease [published correction appears in Cell Death Differ. ;31(8):1099. doi: 10.1038\/s41418-024-01290-w.]. Cell Death Differ. 2021;28(5):1548\u20131562. https:\/\/doi.org\/10.1038\/s41418-020-00685-9","DOI":"10.1038\/s41418-020-00685-9"},{"issue":"1","key":"4641_CR13","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/antiox10010021","volume":"10","author":"A Signorile","year":"2020","unstructured":"Signorile A, Ferretta A, Ruggieri M et al (2020) Mitochondria, oxidative Stress, cAMP signalling and apoptosis: a crossroads in lymphocytes of multiple Sclerosis, a possible role of nutraceutics. Antioxid (Basel) 10(1):21. https:\/\/doi.org\/10.3390\/antiox10010021","journal-title":"Antioxid (Basel)"},{"issue":"Pt 1","key":"4641_CR14","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.bbrc.2022.10.013","volume":"636","author":"S Ji-Wei","year":"2022","unstructured":"Ji-Wei S, Zi-Ying L, Xiang T, Yang Y, Ju-Fen Z, Qing-Hua Z (2022) CNTF induces Clcf1 in astrocytes to promote the differentiation of oligodendrocyte precursor cells. Biochem Biophys Res Commun 636(Pt 1):170\u2013177. https:\/\/doi.org\/10.1016\/j.bbrc.2022.10.013","journal-title":"Biochem Biophys Res Commun"},{"issue":"12","key":"4641_CR15","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1093\/jpp\/rgae086","volume":"76","author":"H Sun","year":"2024","unstructured":"Sun H et al (2024) Mesenchymal stem cell-derived Exosomal microRNA-367-3p mitigates lower limb ischemia\/reperfusion injury in mouse skeletal muscle via EZH2 targeting. J Pharm Pharmacol 76(12):1634\u20131646","journal-title":"J Pharm Pharmacol"},{"issue":"6","key":"4641_CR16","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1177\/0271678X19858637","volume":"40","author":"F Tabet","year":"2020","unstructured":"Tabet F, Lee S, Zhu W et al (2020) microRNA-367-3p regulation of GPRC5A is suppressed in ischemic stroke. J Cereb Blood Flow Metab 40(6):1300\u20131315. https:\/\/doi.org\/10.1177\/0271678X19858637","journal-title":"J Cereb Blood Flow Metab"},{"key":"4641_CR17","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12974-015-0424-3","volume":"12","author":"B Yuan","year":"2015","unstructured":"Yuan B et al (2015) MicroRNA367 negatively regulates the inflammatory response of microglia by targeting IRAK4 in intracerebral hemorrhage. J Neuroinflamm 12:206","journal-title":"J Neuroinflamm"},{"key":"4641_CR18","doi-asserted-by":"publisher","first-page":"114593","DOI":"10.1016\/j.biopha.2023.114593","volume":"162","author":"J Fan","year":"2023","unstructured":"Fan J, Han Y, Sun H et al (2023) Mesenchymal stem cell-derived Exosomal microRNA-367-3p alleviates experimental autoimmune encephalomyelitis via Inhibition of microglial ferroptosis by targeting EZH2. Biomed Pharmacother 162:114593. https:\/\/doi.org\/10.1016\/j.biopha.2023.114593","journal-title":"Biomed Pharmacother"},{"key":"4641_CR19","doi-asserted-by":"publisher","first-page":"101911","DOI":"10.1016\/j.redox.2021.101911","volume":"41","author":"X Han","year":"2021","unstructured":"Han X, Zhao S, Song H et al (2021) Kaempferol alleviates LD-mitochondrial damage by promoting autophagy: implications in parkinson\u2019s disease. Redox Biol 41:101911. https:\/\/doi.org\/10.1016\/j.redox.2021.101911","journal-title":"Redox Biol"},{"key":"4641_CR20","doi-asserted-by":"publisher","first-page":"114387","DOI":"10.1016\/j.intimp.2025.114387","volume":"152","author":"S Li","year":"2025","unstructured":"Li S, Wang S, Zhang L et al (2025) Research progress on pharmacokinetics, anti-inflammatory and Immunomodulatory effects of Kaempferol. Int Immunopharmacol 152:114387. https:\/\/doi.org\/10.1016\/j.intimp.2025.114387","journal-title":"Int Immunopharmacol"},{"key":"4641_CR21","doi-asserted-by":"publisher","first-page":"113951","DOI":"10.1016\/j.intimp.2024.113951","volume":"147","author":"L Wang","year":"2025","unstructured":"Wang L, Gu T, Yu C et al (2025) Kaempferol attenuates experimental autoimmune neuritis through TNFR1\/JNK\/p38 signaling pathway Inhibition. Int Immunopharmacol 147:113951. https:\/\/doi.org\/10.1016\/j.intimp.2024.113951","journal-title":"Int Immunopharmacol"},{"key":"4641_CR22","doi-asserted-by":"publisher","first-page":"114592","DOI":"10.1016\/j.intimp.2025.114592","volume":"154","author":"L Liu","year":"2025","unstructured":"Liu L, Zhao Y, Bu J et al (2025) Baicalin and Kaempferol alleviates cuprizone-induced demyelination and microglial activation by inhibiting the STAT3 and NF-\u03baB signaling pathways. Int Immunopharmacol 154:114592. https:\/\/doi.org\/10.1016\/j.intimp.2025.114592","journal-title":"Int Immunopharmacol"},{"issue":"12","key":"4641_CR23","doi-asserted-by":"publisher","first-page":"e14375","DOI":"10.1111\/jfbc.14375","volume":"46","author":"HR Nejabati","year":"2022","unstructured":"Nejabati HR, Roshangar L (2022) Kaempferol as a potential neuroprotector in alzheimer\u2019s disease. J Food Biochem 46(12):e14375. https:\/\/doi.org\/10.1111\/jfbc.14375","journal-title":"J Food Biochem"},{"issue":"7","key":"4641_CR24","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert N, Hurst V, Ahluwalia A et al (2020) The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol 18(7):e3000410. https:\/\/doi.org\/10.1371\/journal.pbio.3000410","journal-title":"PLoS Biol"},{"issue":"9","key":"4641_CR25","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1002\/iub.2099","volume":"71","author":"OS El-Deeb","year":"2019","unstructured":"El-Deeb OS, Ghanem HB, El\u2010Esawy RO, Sadek MT (2019) The modulatory effects of luteolin on cyclic AMP\/Ciliary neurotrophic factor signaling pathway in experimentally induced autoimmune encephalomyelitis. IUBMB Life 71(9):1401\u20131408. https:\/\/doi.org\/10.1002\/iub.2099","journal-title":"IUBMB Life"},{"key":"4641_CR26","doi-asserted-by":"publisher","unstructured":"Yang YL, Cheng X, Li WH, Liu M, Wang YH, Du GH (2019) Kaempferol attenuates LPS-induced striatum injury in mice involving anti-neuroinflammation, maintaining BBB integrity, and down-regulating the HMGB1\/TLR4 pathway. Int J Mol Sci 20(3):491. https:\/\/doi.org\/10.3390\/ijms20030491","DOI":"10.3390\/ijms20030491"},{"key":"4641_CR27","doi-asserted-by":"publisher","first-page":"146361","DOI":"10.1016\/j.brainres.2019.146361","volume":"1722","author":"WH Li","year":"2019","unstructured":"Li WH, Cheng X, Yang YL et al (2019) Kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral ischemia\/reperfusion rats. Brain Res 1722:146361. https:\/\/doi.org\/10.1016\/j.brainres.2019.146361","journal-title":"Brain Res"},{"issue":"Pt A","key":"4641_CR28","doi-asserted-by":"publisher","first-page":"109373","DOI":"10.1016\/j.intimp.2022.109373","volume":"113","author":"X Ma","year":"2022","unstructured":"Ma X, Wang S, Li C et al (2022) Baicalein inhibits the polarization of microglia\/macrophages to the M1 phenotype by targeting STAT1 in EAE mice. Int Immunopharmacol 113(Pt A):109373. https:\/\/doi.org\/10.1016\/j.intimp.2022.109373","journal-title":"Int Immunopharmacol"},{"key":"4641_CR29","doi-asserted-by":"publisher","unstructured":"Bradford M (1976) M.A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. https:\/\/doi.org\/10.1016\/0003-2697(76)90527-3","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"4641_CR30","doi-asserted-by":"publisher","unstructured":"Ellman G. L. (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82(1):70\u201377. https:\/\/doi.org\/10.1016\/0003-9861(59)90090-6","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"4641_CR31","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","volume":"95","author":"H Ohkawa","year":"1979","unstructured":"Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351\u2013358. https:\/\/doi.org\/10.1016\/0003-2697(79)90738-3","journal-title":"Anal Biochem"},{"key":"4641_CR32","doi-asserted-by":"publisher","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2009\u2013\u2009\u2206\u2206CT method. Methods 25(4): 402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262","DOI":"10.1006\/meth.2001.1262"},{"key":"4641_CR33","doi-asserted-by":"publisher","first-page":"1059833","DOI":"10.3389\/fimmu.2022.1059833","volume":"13","author":"PA McCombe","year":"2022","unstructured":"McCombe PA, Greer JM (2022) Effects of biological sex and pregnancy in experimental autoimmune encephalomyelitis: it\u2019s complicated. Front Immunol 13:1059833. https:\/\/doi.org\/10.3389\/fimmu.2022.1059833","journal-title":"Front Immunol"},{"issue":"9","key":"4641_CR34","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1038\/s41418-023-01195-0","volume":"30","author":"E Van San","year":"2023","unstructured":"Van San E, Debruyne AC, Veeckmans G et al (2023) Ferroptosis contributes to multiple sclerosis and its pharmacological targeting suppresses experimental disease progression. Cell Death Differ 30(9):2092\u20132103. https:\/\/doi.org\/10.1038\/s41418-023-01195-0","journal-title":"Cell Death Differ"},{"key":"4641_CR35","doi-asserted-by":"publisher","unstructured":"Bj\u00f8rklund G, Wallace DR, Hangan T et al (2025) Cerebral iron accumulation in multiple sclerosis: pathophysiology and therapeutic implications. Autoimmun Rev 24(4):103741. https:\/\/doi.org\/10.1016\/j.autrev.2025.103741. Epub 2025 Jan 3. PMID: 39756528","DOI":"10.1016\/j.autrev.2025.103741"},{"issue":"1","key":"4641_CR36","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41423-022-00941-7","volume":"20","author":"AR White","year":"2023","unstructured":"White AR (2023) Ferroptosis drives immune-mediated neurodegeneration in multiple sclerosis. Cell Mol Immunol 20(1):112\u2013113. https:\/\/doi.org\/10.1038\/s41423-022-00941-7","journal-title":"Cell Mol Immunol"},{"key":"4641_CR37","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1038\/s41423-022-00883-0","volume":"19","author":"J Luoqian","year":"2022","unstructured":"Luoqian J, Yang W, Ding X et al (2022) Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis. Cell Mol Immunol 19:913\u2013924. https:\/\/doi.org\/10.1038\/s41423-022-00883-0","journal-title":"Cell Mol Immunol"},{"key":"4641_CR38","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s11481-022-10056-5","volume":"17","author":"J Wang","year":"2022","unstructured":"Wang J, Nan Y, Liu M et al (2022) The role of CD4+ T cells in the immunotherapy of brain disease by secreting different cytokines. J Neuroimmune Pharmacol 17:409\u2013422. https:\/\/doi.org\/10.1007\/s11481-022-10056-5","journal-title":"J Neuroimmune Pharmacol"},{"issue":"4","key":"4641_CR39","doi-asserted-by":"publisher","first-page":"395","DOI":"10.3390\/antiox13040395","volume":"13","author":"Y Xu","year":"2024","unstructured":"Xu Y, Jia B, Li J, Li Q, Luo C (2024) The interplay between ferroptosis and neuroinflammation in central neurological disorders. Antioxidants 13(4):395. https:\/\/doi.org\/10.3390\/antiox13040395","journal-title":"Antioxidants"},{"key":"4641_CR40","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-60006-7_3","volume-title":"Neuroimmune diseases","author":"A Pourgholaminejad","year":"2024","unstructured":"Pourgholaminejad A, Tahmasebinia F (2024) Th17-Mediated immune responses in pathogenesis of neuroinflammatory disorders. In: Mitoma H, Manto M (eds) Neuroimmune diseases. Springer, Cham. https:\/\/doi.org\/10.1007\/978-3-031-60006-7_3"},{"key":"4641_CR41","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1007\/s11011-020-00648-6","volume":"36","author":"S Ghafouri-Fard","year":"2021","unstructured":"Ghafouri-Fard S, Honarmand K, Taheri M (2021) A comprehensive review on the role of chemokines in the pathogenesis of multiple sclerosis. Metab Brain Dis 36:375\u2013406. https:\/\/doi.org\/10.1007\/s11011-020-00648-6","journal-title":"Metab Brain Dis"},{"key":"4641_CR42","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s12964-024-01509-w","volume":"22","author":"X Xu","year":"2024","unstructured":"Xu X, Han Y, Zhang B et al (2024) Understanding immune microenvironment alterations in the brain to improve the diagnosis and treatment of diverse brain diseases. Cell Commun Signal 22:132. https:\/\/doi.org\/10.1186\/s12964-024-01509-w","journal-title":"Cell Commun Signal"},{"issue":"5","key":"4641_CR43","doi-asserted-by":"publisher","first-page":"527","DOI":"10.3390\/antiox14050527","volume":"14","author":"N Abdukarimov","year":"2025","unstructured":"Abdukarimov N, Kokabi K, Kunz J (2025) Ferroptosis and iron homeostasis: molecular mechanisms and neurodegenerative disease implications. Antioxidants 14(5):527. https:\/\/doi.org\/10.3390\/antiox14050527","journal-title":"Antioxidants"},{"key":"4641_CR44","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/s41419-024-06807-2","volume":"15","author":"L Zeng","year":"2024","unstructured":"Zeng L, Yang K, Yu G et al (2024) Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases. Cell Death Dis 15:481. https:\/\/doi.org\/10.1038\/s41419-024-06807-2","journal-title":"Cell Death Dis"},{"issue":"7","key":"4641_CR45","doi-asserted-by":"publisher","first-page":"923","DOI":"10.3390\/biom11070923","volume":"11","author":"Y Yuan","year":"2021","unstructured":"Yuan Y, Zhai Y, Chen J et al (2021) Kaempferol ameliorates oxygen-glucose deprivation\/reoxygenation-induced neuronal ferroptosis by activating Nrf2\/SLC7A11\/GPX4 axis. Biomolecules 11(7):923. https:\/\/doi.org\/10.3390\/biom11070923","journal-title":"Biomolecules"},{"key":"4641_CR46","doi-asserted-by":"publisher","unstructured":"Li Q, Yang X, Li T Natural flavonoids from herbs and nutraceuticals as ferroptosis inhibitors in central nervous system diseases: current preclinical evidence and future perspectives. Front Pharmacol 2025, 16:1570069. https:\/\/doi.org\/10.3389\/fphar.2025.1570069","DOI":"10.3389\/fphar.2025.1570069"},{"issue":"1","key":"4641_CR47","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.bbrc.2006.10.016","volume":"351","author":"M Hirano","year":"2006","unstructured":"Hirano M, Zang L, Oka T et al (2006) Novel reciprocal regulation of cAMP signaling and apoptosis by orphan G-protein-coupled receptor GPRC5A gene expression. Biochem Biophys Res Commun 351(1):185\u2013191. https:\/\/doi.org\/10.1016\/j.bbrc.2006.10.016","journal-title":"Biochem Biophys Res Commun"},{"issue":"3","key":"4641_CR48","doi-asserted-by":"publisher","first-page":"140","DOI":"10.4103\/ejpi.EJPI-D-24-00103","volume":"68","author":"Q He","year":"2025","unstructured":"He Q, Tian X, Zhang Y, Mu Q (2025) MiR-367-3p alleviates oxidative stress injury in the Ischemia\/Reperfusion injury cell model by targeting nicotinamide adenine dinucleotide phosphate oxidase 4-mediated Keap1\/Nrf2\/ARE pathway. J Physiol Investig 68(3):140\u2013149. https:\/\/doi.org\/10.4103\/ejpi.EJPI-D-24-00103","journal-title":"J Physiol Investig"},{"key":"4641_CR49","doi-asserted-by":"publisher","first-page":"111065","DOI":"10.1016\/j.brainresbull.2024.111065","volume":"217","author":"C Wei","year":"2024","unstructured":"Wei C (2024) The role of glutathione peroxidase 4 in neuronal ferroptosis and its therapeutic potential in ischemic and hemorrhagic stroke. Brain Res Bull 217:111065. https:\/\/doi.org\/10.1016\/j.brainresbull.2024.111065","journal-title":"Brain Res Bull"},{"key":"4641_CR50","doi-asserted-by":"publisher","first-page":"119748","DOI":"10.1016\/j.jep.2025.119748","volume":"347","author":"H Wang","year":"2025","unstructured":"Wang H, Zou J, Li Y et al (2025) Tripterygium glycoside tablets and triptolide alleviate experimental autoimmune encephalomyelitis mice involving the PACAP\/cAMP signaling pathway. J Ethnopharmacol 347:119748. https:\/\/doi.org\/10.1016\/j.jep.2025.119748","journal-title":"J Ethnopharmacol"},{"issue":"3","key":"4641_CR51","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1021\/acschemneuro.1c00830","volume":"13","author":"D Zhao","year":"2022","unstructured":"Zhao D, Zhang M, Yang L, Zeng M (2022) GPR68 improves nerve damage and myelination in an immature rat model induced by Sevoflurane anesthesia by activating cAMP\/CREB to mediate BDNF. ACS Chem Neurosci 13(3):423\u2013431. https:\/\/doi.org\/10.1021\/acschemneuro.1c00830","journal-title":"ACS Chem Neurosci"},{"key":"4641_CR52","doi-asserted-by":"publisher","first-page":"1401273","DOI":"10.3389\/fphar.2024.1401273","volume":"15","author":"J Thaweewattanodom","year":"2024","unstructured":"Thaweewattanodom J, Deachapunya C, Poonyachoti S (2024) Kaempferol activates chloride secretion via the cAMP\/PKA signaling pathway and expression of CFTR in T84 cells. Front Pharmacol 15:1401273. https:\/\/doi.org\/10.3389\/fphar.2024.1401273","journal-title":"Front Pharmacol"},{"key":"4641_CR53","doi-asserted-by":"publisher","unstructured":"Kim J, Kaang BK (2023) Cyclic AMP response element-binding protein (CREB) transcription factor in astrocytic synaptic communication. Front Synaptic Neurosci 14:1059918. https:\/\/doi.org\/10.3389\/fnsyn.2022.1059918. PMID: 36685081; PMCID: PMC9845270","DOI":"10.3389\/fnsyn.2022.1059918"}],"container-title":["Neurochemical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04641-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11064-025-04641-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-025-04641-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:44:07Z","timestamp":1781628247000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11064-025-04641-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["4641"],"URL":"https:\/\/doi.org\/10.1007\/s11064-025-04641-2","relation":{},"ISSN":["0364-3190","1573-6903"],"issn-type":[{"value":"0364-3190","type":"print"},{"value":"1573-6903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]},"assertion":[{"value":"27 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This research adhered to the guidelines of the National Institutes of Health for the care and use of laboratory animals (NIH Publications No. 8023, revised 1996) and was approved by the Research Ethics Committee, Faculty of Medicine, Tanta University, Egypt (Approval No. 36264PR1221\/5\/25).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"All authors agree to publication.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}}],"article-number":"45"}}