{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:29:11Z","timestamp":1794004151391,"version":"4.8.0"},"reference-count":119,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-75-00035"],"award-info":[{"award-number":["22-75-00035"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Spinal cord injury (SCI) leads to significant functional impairments below the level of the injury, and astrocytes play a crucial role in the pathophysiology of SCI. Astrocytes undergo changes and form a glial scar after SCI, which has traditionally been viewed as a barrier to axonal regeneration and functional recovery. Astrocytes activate intracellular signaling pathways, including nuclear factor \u03baB (NF-\u03baB) and Janus kinase-signal transducers and activators of transcription (JAK\/STAT), in response to external stimuli. NF-\u03baB and STAT3 are transcription factors that play a pivotal role in initiating gene expression related to astrogliosis. The JAK\/STAT signaling pathway is essential for managing secondary damage and facilitating recovery processes post-SCI: inflammation, glial scar formation, and astrocyte survival. NF-\u03baB activation in astrocytes leads to the production of pro-inflammatory factors by astrocytes. NF-\u03baB and STAT3 signaling pathways are interconnected: NF-\u03baB activation in astrocytes leads to the release of interleukin-6 (IL-6), which interacts with the IL-6 receptor and initiates STAT3 activation. By modulating astrocyte responses, these pathways offer promising avenues for enhancing recovery outcomes, illustrating the crucial need for further investigation into their mechanisms and therapeutic applications in SCI treatment.<\/jats:p>","DOI":"10.3390\/cells13070581","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T13:16:41Z","timestamp":1711459001000},"page":"581","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":163,"title":["NF-\u03baB and JAK\/STAT Signaling Pathways as Crucial Regulators of Neuroinflammation and Astrocyte Modulation in Spinal Cord Injury"],"prefix":"10.3390","volume":"13","author":[{"given":"Tatyana","family":"Ageeva","sequence":"first","affiliation":[{"name":"OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9427-5739","authenticated-orcid":false,"given":"Albert","family":"Rizvanov","sequence":"additional","affiliation":[{"name":"OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"},{"name":"Division of Medical and Biological Sciences, Tatarstan Academy of Sciences, 420111 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Mukhamedshina","sequence":"additional","affiliation":[{"name":"OpenLab Gene and Cell Technology, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia"},{"name":"Department of Histology, Cytology and Embryology, Kazan State Medical University, 420012 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nature09611","article-title":"Developmental genetics of vertebrate glial-cell specification","volume":"468","author":"Rowitch","year":"2010","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.immuni.2017.06.006","article-title":"Reactive Astrocytes: Production, Function, and Therapeutic Potential","volume":"46","author":"Liddelow","year":"2017","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","article-title":"Astrocyte Crosstalk in CNS Inflammation","volume":"108","author":"Linnerbauer","year":"2020","journal-title":"Neuron"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.tins.2009.08.002","article-title":"Molecular dissection of reactive astrogliosis and glial scar formation","volume":"32","author":"Sofroniew","year":"2009","journal-title":"Trends Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Perez-Gianmarco, L., and Kukley, M. (2023). Understanding the Role of the Glial Scar through the Depletion of Glial Cells after Spinal Cord Injury. Cells, 12.","DOI":"10.20944\/preprints202305.1822.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"29681","DOI":"10.1074\/jbc.M201517200","article-title":"MAP kinase cascades are activated in astrocytes and preadipocytes by 15-deoxy-Delta(12-14)-prostaglandin J(2) and the thiazolidinedione ciglitazone through peroxisome proliferator activator receptor gamma-independent mechanisms involving reactive oxygenated species","volume":"277","author":"Lennon","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bbamcr.2005.05.009","article-title":"Signaling via NF-kappaB in the nervous system","volume":"1745","author":"Kaltschmidt","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhou, Z., Ikegaya, Y., and Koyama, R. (2019). The Astrocytic cAMP Pathway in Health and Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030779"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1523\/JNEUROSCI.18-09-03251.1998","article-title":"Traumatic spinal cord injury induces nuclear factor-kappaB activation","volume":"18","author":"Bethea","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7231","DOI":"10.1523\/JNEUROSCI.1709-08.2008","article-title":"STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury","volume":"28","author":"Herrmann","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16975","DOI":"10.1073\/pnas.1315862110","article-title":"STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor to EGF receptor","volume":"110","author":"Wang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1523\/JNEUROSCI.3457-15.2016","article-title":"Astrocytic GAP43 Induced by the TLR4\/NF-\u03baB\/STAT3 Axis Attenuates Astrogliosis-Mediated Microglial Activation and Neurotoxicity","volume":"36","author":"Hung","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ceb.2015.02.004","article-title":"Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system","volume":"32","author":"Hol","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1146\/annurev-med-051113-024537","article-title":"The JAK-STAT pathway: Impact on human disease and therapeutic intervention","volume":"66","author":"Schwartz","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hu, Q., Bian, Q., Rong, D., Wang, L., Song, J., Huang, H.S., Zeng, J., Mei, J., and Wang, P.Y. (2023). JAK\/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens. Front. Bioeng. Biotechnol., 11.","DOI":"10.3389\/fbioe.2023.1110765"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1080\/15384101.2019.1667189","article-title":"Blocking Notch signal pathway suppresses the activation of neurotoxic A1 astrocytes after spinal cord injury","volume":"18","author":"Qian","year":"2019","journal-title":"Cell Cycle"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9494352","DOI":"10.1155\/2020\/9494352","article-title":"Reactive Astrogliosis: Implications in Spinal Cord Injury Progression and Therapy","volume":"2020","author":"Li","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1002\/glia.22953","article-title":"Traumatically injured astrocytes release a proteomic signature modulated by STAT3-dependent cell survival","volume":"64","author":"Levine","year":"2016","journal-title":"Glia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.3389\/fimmu.2019.01043","article-title":"Cellular Specificity of NF-\u03baB Function in the Nervous System","volume":"10","author":"Dresselhaus","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"716469","DOI":"10.3389\/fimmu.2021.716469","article-title":"NF-\u03baB: At the Borders of Autoimmunity and Inflammation","volume":"12","author":"Barnabei","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1038\/labinvest.3780341","article-title":"Specific deficiency in nuclear factor-kappaB activation in neurons of the central nervous system","volume":"81","author":"Jarosinski","year":"2001","journal-title":"Lab. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0893-133X(01)00292-5","article-title":"The Increase in TNF-\u03b1 Levels Is Implicated in NF-\u03baB Activation and Inducible Nitric Oxide Synthase Expression in Brain Cortex after Immobilization Stress","volume":"26","author":"Madrigal","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1002\/art.20601","article-title":"Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals","volume":"50","author":"Agarwal","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9159","DOI":"10.1523\/JNEUROSCI.0302-11.2011","article-title":"Nuclear factor-\u03baB contributes to neuron-dependent induction of glutamate transporter-1 expression in astrocytes","volume":"31","author":"Ghosh","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2623","DOI":"10.4049\/jimmunol.178.5.2623","article-title":"The JAK-STAT signaling pathway: Input and output integration","volume":"178","author":"Murray","year":"2007","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1600-065X.2008.00754.x","article-title":"Janus kinases in immune cell signaling","volume":"228","author":"Ghoreschi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/nrd4088","article-title":"Therapeutic modulators of STAT signalling for human diseases","volume":"12","author":"Miklossy","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1073\/pnas.91.11.4806","article-title":"Stat3 and Stat4: Members of the family of signal transducers and activators of transcription","volume":"91","author":"Zhong","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Diop, A., Santorelli, D., Malagrin\u00f2, F., Nardella, C., Pennacchietti, V., Pagano, L., Marcocci, L., Pietrangeli, P., Gianni, S., and Toto, A. (2022). SH2 Domains: Folding, Binding and Therapeutical Approaches. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415944"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3892\/br.2014.401","article-title":"The role of the JAK-STAT pathway in neural stem cells, neural progenitor cells and reactive astrocytes after spinal cord injury","volume":"3","author":"Wang","year":"2015","journal-title":"Biomed. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/(SICI)1098-1136(200005)30:3<253::AID-GLIA5>3.0.CO;2-O","article-title":"Activation of the JAK\/STAT pathway following transient focal cerebral ischemia: Signaling through Jak1 and Stat3 in astrocytes","volume":"30","author":"Justicia","year":"2000","journal-title":"Glia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1126\/science.278.5337.477","article-title":"Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway","volume":"278","author":"Bonni","year":"1997","journal-title":"Science"},{"key":"ref_35","first-page":"e22925","article-title":"The role of JAK-STAT signaling within the CNS","volume":"2","author":"Nicolas","year":"2013","journal-title":"JAKSTAT"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Huang, T., Fakurazi, S., Cheah, P.S., and Ling, K.H. (2023). REST Targets JAK-STAT and HIF-1 Signaling Pathways in Human Down Syndrome Brain and Neural Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24129980"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/j.1471-4159.2005.03559.x","article-title":"Activation of JAK\/STAT signalling in neurons following spinal cord injury in mice","volume":"96","author":"Yamauchi","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1042\/BJ20100774","article-title":"Transforming JAK1 mutations exhibit differential signalling, FERM domain requirements and growth responses to interferon-\u03b3","volume":"432","author":"Gordon","year":"2010","journal-title":"Biochem. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1139\/bcb-2019-0088","article-title":"Mitochondrial dysfunction regulates the JAK-STAT pathway via LKB1-mediated AMPK activation ER-stress-independent manner","volume":"98","author":"Kim","year":"2020","journal-title":"Biochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.pain.2013.03.026","article-title":"Inhibition of IL-6 signaling: A novel therapeutic approach to treating spinal cord injury pain","volume":"154","author":"Guptarak","year":"2013","journal-title":"Pain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1097\/NEN.0000000000000011","article-title":"The regulation of reactive changes around multiple sclerosis lesions by phosphorylated signal transducer and activator of transcription","volume":"72","author":"Lu","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lu, Y., He, M., Zhang, Y., Xu, S., Zhang, L., He, Y., Chen, C., Liu, C., Pi, H., and Yu, Z. (2014). Differential pro-inflammatory responses of astrocytes and microglia involve STAT3 activation in response to 1800 MHz radiofrequency fields. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0108318"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Toral-Rios, D., Pati\u00f1o-L\u00f3pez, G., G\u00f3mez-Lira, G., Guti\u00e9rrez, R., Becerril-P\u00e9rez, F., Rosales-C\u00f3rdova, A., Le\u00f3n-Contreras, J.C., Hern\u00e1ndez-Pando, R., Le\u00f3n-Rivera, I., and Soto-Cruz, I. (2020). Activation of STAT3 Regulates Reactive Astrogliosis and Neuronal Death Induced by A\u03b2O Neurotoxicity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207458"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jocn.2004.06.011","article-title":"Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat","volume":"12","author":"Yang","year":"2005","journal-title":"J. Clin. Neurosci."},{"key":"ref_45","first-page":"137","article-title":"Regulation of inflammatory cytokines for spinal cord injury recovery","volume":"36","author":"Lin","year":"2021","journal-title":"Histol. Histopathol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Gombos, G., N\u00e9meth, N., P\u00f6s, O., Styk, J., Bugly\u00f3, G., Szemes, T., Danihel, L., Nagy, B., Balogh, I., and Solt\u00e9sz, B. (2023). New Possible Ways to Use Exosomes in Diagnostics and Therapy via JAK\/STAT Pathways. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071904"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"111367","DOI":"10.1016\/j.intimp.2023.111367","article-title":"IL-11 ameliorates oxidative stress damage in neurons after spinal cord injury by activating the JAK\/STAT signaling pathway","volume":"127","author":"Sun","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1182\/blood.V86.4.1243.bloodjournal8641243","article-title":"Interleukin-6 family of cytokines and gp130","volume":"86","author":"Kishimoto","year":"1995","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1523\/JNEUROSCI.20-11-04081.2000","article-title":"Ciliary neurotrophic factor and stress stimuli activate the Jak-STAT pathway in retinal neurons and glia","volume":"20","author":"Peterson","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12079-012-0186-y","article-title":"Signaling network of Oncostatin M pathway","volume":"7","author":"Dey","year":"2013","journal-title":"J. Cell Commun. Signal."},{"key":"ref_51","first-page":"131","article-title":"The JAK-STAT pathway in hypertrophic stress signaling and genomic stress response","volume":"1","author":"Wagner","year":"2012","journal-title":"JAKSTAT"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1359-6101(98)80005-1","article-title":"Signaling mechanisms through gp130: A model of the cytokine system","volume":"8","author":"Hirano","year":"1997","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nm1425","article-title":"Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury","volume":"12","author":"Okada","year":"2006","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.expneurol.2014.06.013","article-title":"Expression of suppressor of cytokine signaling-3 (SOCS3) and its role in neuronal death after complete spinal cord injury","volume":"261","author":"Park","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.neures.2005.01.004","article-title":"Stage-dependent fate determination of neural precursor cells in mouse forebrain","volume":"51","author":"Hirabayashi","year":"2005","journal-title":"Neurosci. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4161\/cam.3.1.7602","article-title":"Dynamic signaling for neural stem cell fate determination","volume":"3","author":"Wen","year":"2009","journal-title":"Cell Adhes. Migr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1093\/brain\/awr025","article-title":"JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic pain maintenance in rats","volume":"134","author":"Tsuda","year":"2011","journal-title":"Brain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"33172","DOI":"10.1074\/jbc.M606940200","article-title":"Elevated activity of STAT3C due to higher DNA binding affinity of phosphotyrosine dimer rather than covalent dimer formation","volume":"281","author":"Li","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/j.1471-4159.2011.07610.x","article-title":"STAT3 signaling after traumatic brain injury","volume":"120","author":"Oliva","year":"2012","journal-title":"J. Neurochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1007\/s11064-011-0576-1","article-title":"Role of signal transducer and activator of transcription-3 in up-regulation of GFAP after epilepsy","volume":"36","author":"Xu","year":"2011","journal-title":"Neurochem. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Natarajan, R., Singal, V., Benes, R., Gao, J., Chan, H., Chen, H., Yu, Y., Zhou, J., and Wu, P. (2014). STAT3 modulation to enhance motor neuron differentiation in human neural stem cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0100405"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1523\/JNEUROSCI.3516-14.2015","article-title":"The JAK\/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer\u2019s and Huntington\u2019s diseases","volume":"35","author":"Aubry","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.expneurol.2016.08.002","article-title":"Mitochondrial STAT3 is negatively regulated by SOCS3 and upregulated after spinal cord injury","volume":"284","author":"Park","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hong, S., and Song, M.R. (2014). STAT3 but not STAT1 is required for astrocyte differentiation. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086851"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/cr.2014.154","article-title":"STAT5 programs a distinct subset of GM-CSF-producing T helper cells that is essential for autoimmune neuroinflammation","volume":"24","author":"Sheng","year":"2014","journal-title":"Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"679","DOI":"10.5483\/BMBRep.2014.47.12.018","article-title":"GM-CSF reduces expression of chondroitin sulfate proteoglycan (CSPG) core proteins in TGF-\u03b2-treated primary astrocytes","volume":"47","author":"Choi","year":"2014","journal-title":"BMB Rep."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Alqawlaq, S., Livne-Bar, I., Williams, D., D\u2019Ercole, J., Leung, S.W., Chan, D., Tuccitto, A., Datti, A., Wrana, J.L., and Corbett, A.H. (2021). An endogenous PI3K interactome promoting astrocyte-mediated neuroprotection identifies a novel association with RNA-binding protein ZC3H14. J. Biol. Chem., 296.","DOI":"10.1074\/jbc.RA120.015389"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1276445","DOI":"10.3389\/fimmu.2023.1276445","article-title":"Regulation of the JAK\/STAT signaling pathway in spinal cord injury: An updated review","volume":"14","author":"Guo","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.injury.2010.05.027","article-title":"Evaluation of protective effects of the alpha lipoic acid after spinal cord injury: An animal study","volume":"41","author":"Tas","year":"2010","journal-title":"Injury"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1083\/jcb.201610102","article-title":"Regulation of RhoA by STAT3 coordinates glial scar formation","volume":"216","author":"Mukaino","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neuroscience.2011.03.063","article-title":"MicroRNA dysregulation following spinal cord contusion: Implications for neural plasticity and repair","volume":"186","author":"Strickland","year":"2011","journal-title":"Neuroscience"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Oeckinghaus, A., and Ghosh, S. (2009). The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol., 1.","DOI":"10.1101\/cshperspect.a000034"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.it.2022.07.004","article-title":"NF-\u03baB: Blending metabolism, immunity, and inflammation","volume":"43","author":"Capece","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1074\/jbc.275.7.4719","article-title":"Inhibition of the RelA(p65) NF-kappaB subunit by Egr-1","volume":"275","author":"Chapman","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1600-065X.2012.01097.x","article-title":"NF-\u03baB regulation: Lessons from structures","volume":"246","author":"Ghosh","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"239368","DOI":"10.1155\/2012\/239368","article-title":"A key role for NF-\u03baB transcription factor c-Rel in T-lymphocyte-differentiation and effector functions","volume":"2012","author":"Visekruna","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"823821","DOI":"10.1155\/2010\/823821","article-title":"Regulation of IkappaBalpha function and NF-kappaB signaling: AEBP1 is a novel proinflammatory mediator in macrophages","volume":"2010","author":"Majdalawieh","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"45225","DOI":"10.1074\/jbc.M105865200","article-title":"IkappaBbeta, but not IkappaBalpha, functions as a classical cytoplasmic inhibitor of NF-kappaB dimers by masking both NF-kappaB nuclear localization sequences in resting cells","volume":"276","author":"Malek","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1074\/jbc.M207515200","article-title":"p105.Ikappa Bgamma and prototypical Ikappa Bs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-kappa B","volume":"278","author":"Moorthy","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.molcel.2009.04.033","article-title":"The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes","volume":"34","author":"Savinova","year":"2009","journal-title":"Mol. Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.jmb.2010.10.055","article-title":"The RelA nuclear localization signal folds upon binding to I\u03baB\u03b1","volume":"405","author":"Cervantes","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.3389\/fimmu.2018.01849","article-title":"Tumor Necrosis Factor Receptor-Associated Factor Regulation of Nuclear Factor \u03baB and Mitogen-Activated Protein Kinase Pathways","volume":"9","author":"Shi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1101\/gad.13.19.2514","article-title":"Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis","volume":"13","author":"Lin","year":"1999","journal-title":"Genes Dev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1083\/jcb.200204039","article-title":"Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different mechanisms","volume":"157","author":"Morgan","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11778","DOI":"10.1073\/pnas.0711122105","article-title":"Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation","volume":"105","author":"Mahoney","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kaltschmidt, B., and Kaltschmidt, C. (2009). NF-kappaB in the nervous system. Cold Spring Harb. Perspect Biol., 1.","DOI":"10.1101\/cshperspect.a001271"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1002\/embr.201337983","article-title":"The I\u03baB kinase complex in NF-\u03baB regulation and beyond","volume":"15","author":"Hinz","year":"2014","journal-title":"EMBO Rep."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Isra\u00ebl, A. (2010). The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb. Perspect. Biol., 2.","DOI":"10.1101\/cshperspect.a000158"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Huang, W.C., and Hung, M.C. (2013). Beyond NF-\u03baB activation: Nuclear functions of I\u03baB kinase \u03b1. J. Biomed. Sci., 20.","DOI":"10.1186\/1423-0127-20-3"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1083\/jcb.200601065","article-title":"Myosin motor Myo1c and its receptor NEMO\/IKK-gamma promote TNF-alpha-induced serine307 phosphorylation of IRS-1","volume":"173","author":"Nakamori","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/cr.2010.166","article-title":"Deubiquitinases in the regulation of NF-\u03baB signaling","volume":"21","author":"Harhaj","year":"2011","journal-title":"Cell Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/cmi.2011.59","article-title":"Regulation of NF-\u03baB signaling by the A20 deubiquitinase","volume":"9","author":"Shembade","year":"2012","journal-title":"Cell. Mol. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yang, Q., Zhao, J., Chen, D., and Wang, Y. (2021). E3 ubiquitin ligases: Styles, structures and functions. Mol. Biomed., 2.","DOI":"10.1186\/s43556-021-00043-2"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Xie, J., Jin, Y., and Wang, G. (2019). The role of SCF ubiquitin-ligase complex at the beginning of life. Reprod. Biol. Endocrinol., 17.","DOI":"10.1186\/s12958-019-0547-y"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/sj.cdd.4401837","article-title":"Roles for NF-kappaB in nerve cell survival, plasticity, and disease","volume":"13","author":"Mattson","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0169-328X(99)00091-1","article-title":"Characterization of a neuronal kappaB-binding factor distinct from NF-kappaB","volume":"67","author":"Moerman","year":"1999","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.neuroscience.2013.07.013","article-title":"Minimal NF-\u03baB activity in neurons","volume":"250","author":"Listwak","year":"2013","journal-title":"Neuroscience"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/0169-328X(96)00036-8","article-title":"Induction of neuroprotective kappa B-dependent transcription by secreted forms of the Alzheimer\u2019s beta-amyloid precursor","volume":"40","author":"Barger","year":"1996","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1523\/JNEUROSCI.22-19-08466.2002","article-title":"Constitutive nuclear factor-kappa B activity is required for central neuron survival","volume":"22","author":"Bhakar","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnmol.2015.00077","article-title":"NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review","volume":"8","author":"Shih","year":"2015","journal-title":"Front. Mol. Neurosci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1101\/lm.866408","article-title":"c-Rel, an NF-kappaB family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation","volume":"15","author":"Ahn","year":"2008","journal-title":"Learn. Mem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/sj.cdd.4401598","article-title":"NF-kappaB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity","volume":"12","author":"Pizzi","year":"2005","journal-title":"Cell Death Differ."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e96","DOI":"10.1038\/cddis.2010.76","article-title":"The acetylation of RelA in Lys310 dictates the NF-\u03baB-dependent response in post-ischemic injury","volume":"1","author":"Lanzillotta","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/cr.2010.147","article-title":"I\u03baB\u03b2 is a positive and negative regulator of NF-\u03baB activity during inflammation","volume":"20","author":"Kamata","year":"2010","journal-title":"Cell Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1074\/mcp.RA120.002316","article-title":"A Novel Mechanism for NF-\u03baB-activation via I\u03baB-aggregation: Implications for Hepatic Mallory-Denk-Body Induced Inflammation","volume":"19","author":"Liu","year":"2020","journal-title":"Mol. Cell. Proteom."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41392-020-00312-6","article-title":"Targeting NF-\u03baB pathway for the therapy of diseases: Mechanism and clinical study","volume":"5","author":"Yu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"988790","DOI":"10.3389\/fnmol.2022.988790","article-title":"Contributions of extracellular-signal regulated kinase 1\/2 activity to the memory trace","volume":"15","author":"Feld","year":"2022","journal-title":"Front. Mol. Neurosci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neuron.2014.11.018","article-title":"NF\u03baB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer\u2019s disease","volume":"85","author":"Lian","year":"2015","journal-title":"Neuron"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s40478-016-0350-3","article-title":"Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia","volume":"4","author":"Saggu","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Crosio, C., Valle, C., Casciati, A., Iaccarino, C., and Carr\u00ec, M.T. (2011). Astroglial inhibition of NF-\u03baB does not ameliorate disease onset and progression in a mouse model for amyotrophic lateral sclerosis (ALS). PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017187"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Birck, C., Ginolhac, A., Pavlou, M.A.S., Michelucci, A., Heuschling, P., and Grandbarbe, L. (2021). NF-\u03baB and TNF Affect the Astrocytic Differentiation from Neural Stem Cells. Cells, 10.","DOI":"10.3390\/cells10040840"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5041","DOI":"10.1007\/s12035-015-9428-3","article-title":"Inflammation Promotes a Conversion of Astrocytes into Neural Progenitor Cells via NF-\u03baB Activation","volume":"53","author":"Gabel","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.tins.2011.03.001","article-title":"Regulation of neural process growth, elaboration and structural plasticity by NF-\u03baB","volume":"34","author":"Gutierrez","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Mockenhaupt, K., Gonsiewski, A., and Kordula, T. (2021). RelB and Neuroinflammation. Cells, 10.","DOI":"10.3390\/cells10071609"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/S1097-2765(03)00227-2","article-title":"Modulation of NF-kappaB activity by exchange of dimers","volume":"11","author":"Saccani","year":"2003","journal-title":"Mol. Cell."},{"key":"ref_116","first-page":"2941","article-title":"Inflammation, cytokines, the IL-17\/IL-6\/STAT3\/NF-\u03baB axis, and tumorigenesis","volume":"9","author":"Chen","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1172\/JCI10530","article-title":"IL-4 abrogates osteoclastogenesis through STAT6-dependent inhibition of NF-kappaB","volume":"107","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1128\/MCB.24.17.7806-7819.2004","article-title":"NF-kappaB and AP-1 connection: Mechanism of NF-kappaB-dependent regulation of AP-1 activity","volume":"24","author":"Fujioka","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"897","DOI":"10.4161\/cc.4.7.1837","article-title":"The Jak\/Stat pathway: A novel way to regulate PI3K activity","volume":"4","author":"Abell","year":"2005","journal-title":"Cell Cycle"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/7\/581\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:19:06Z","timestamp":1760105946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/7\/581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,26]]},"references-count":119,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["cells13070581"],"URL":"https:\/\/doi.org\/10.3390\/cells13070581","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,26]]}}}