{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:09:44Z","timestamp":1760058584601,"version":"build-2065373602"},"reference-count":107,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Miguel Servet grant","award":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"]}]},{"name":"Instituto de Salud Carlos III (Spanish Ministry of Health)\u2014General Branch Evaluation and Promotion of Health Research","award":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"]}]},{"name":"European Regional Development Fund (ERDF)","award":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"]}]},{"DOI":"10.13039\/501100009068","name":"CONICYT-Doctorado Becas Chile 2015","doi-asserted-by":"publisher","award":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"]}],"id":[{"id":"10.13039\/501100009068","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universidad San Sebasti\u00e1n, Chile","award":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"]}]},{"name":"Institute de Salud Carlos III (Spanish Ministry of Health)","award":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"],"award-info":[{"award-number":["MS16\/00153-CP16\/00153","72160426","USS-FIN-24-PASI-09","PI18\/00213"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Despite the emerging evidence of the role of transcriptional regulators in schizophrenia as key molecular effectors responsible for the dysregulation of multiple biological processes, limited information is available for brain areas that control higher cognitive functions, such as the cerebellum. To identify transcription factors that could control a wide panel of altered proteins in the cerebellar cortex in schizophrenia, we analyzed a dataset obtained using one-shot liquid chromatography\u2013tandem mass spectrometry on the postmortem human cerebellar cortex in chronic schizophrenia (PXD024937 identifier in the ProteomeXchange repository). Our analysis revealed a panel of 11 enriched transcription factors (SP1, KLF7, SP4, EGR1, HNF4A, CTCF, GABPA, NRF1, NFYA, YY1, and MEF2A) that could be controlling 250 altered proteins. The top three significantly enriched transcription factors were SP1, YY1, and EGR1, and the transcription factors with the largest number of targets were SP1, KLF7, and SP4 which belong to the Kr\u00fcppel superfamily. An enrichment in vesicle-mediated transport was found for SP1, KLF7, EGR1, HNF4A, CTCF, and MEF2A targets, while pathways related to signaling, inflammation\/immune responses, apoptosis, and energy were found for SP1 and KLF7 targets. EGR1 targets were enriched in RNA processing, and GABPA and YY1 targets were mainly involved in organelle organization and assembly. This study provides a reduced panel of transcriptional regulators that could impact multiple pathways through the control of a number of targets in the cerebellum in chronic schizophrenia. These findings suggest that this panel of transcription factors could represent key targets for pharmacological interventions in schizophrenia.<\/jats:p>","DOI":"10.3390\/ijms26083653","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T06:18:36Z","timestamp":1744611516000},"page":"3653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional Regulators in the Cerebellum in Chronic Schizophrenia: Novel Possible Targets for Pharmacological Interventions"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3468-0556","authenticated-orcid":false,"given":"Am\u00e9rica","family":"Vera-Montecinos","sequence":"first","affiliation":[{"name":"Psiquiatria Molecular, Parc Sanitari Sant Joan de D\u00e9u, Institut de Recerca Sant Joan de D\u00e9u, Dr. Antoni Pujadas 42, 08830 Sant Boi de Llobregat, Spain"},{"name":"Departamento de Ciencias Biol\u00f3gicas y Qu\u00edmicas, Facultad De Ciencias, Universidad San Sebasti\u00e1n, Sede Tres Pascualas Lientur 1457, Concepci\u00f3n 4080871, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bel\u00e9n","family":"Ramos","sequence":"additional","affiliation":[{"name":"Psiquiatria Molecular, Parc Sanitari Sant Joan de D\u00e9u, Institut de Recerca Sant Joan de D\u00e9u, Dr. Antoni Pujadas 42, 08830 Sant Boi de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Salud Mental, CIBERSAM (Biomedical Network Research Center of Mental Health), Ministry of Economy, Industry and Competitiveness Institute of Health Carlos III, 28029 Madrid, Spain"},{"name":"Faculty of Medicine, University of Vic-Central University of Catalonia, 08500 Vic, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1093\/schbul\/sbx121","article-title":"30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed into the Developmental Risk Factor Model of Psychosis","volume":"43","author":"Murray","year":"2017","journal-title":"Schizophr. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neubiorev.2016.03.017","article-title":"A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis","volume":"65","author":"Davis","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/mp.2012.23","article-title":"Neurodevelopmental model of schizophrenia: Update 2012","volume":"17","author":"Rapoport","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.neubiorev.2021.10.025","article-title":"The dual hit hypothesis of schizophrenia: Evidence from animal models","volume":"131","author":"Guerrin","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_5","first-page":"203","article-title":"Cognitive of \u201cCognitive Dysmetria\u201c as an Integrative Theory of Dysfunction in Cortical- Schizophrenia: A Dysfunction Subcortical\u2014Cerebellar Circuitry?","volume":"24","author":"Andreasen","year":"2018","journal-title":"Network"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S0006-3223(99)00152-3","article-title":"Defining the phenotype of schizophrenia: Cognitive dysmetria and its neural mechanisms","volume":"46","author":"Andreasen","year":"1999","journal-title":"Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.nicl.2017.03.001","article-title":"Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis","volume":"14","author":"Bernard","year":"2017","journal-title":"NeuroImage Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41537-021-00169-w","article-title":"Impaired cerebro-cerebellar white matter connectivity and its associations with cognitive function in patients with schizophrenia","volume":"7","author":"Kim","year":"2021","journal-title":"Schizophrenia"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, P., Ye, E., Jin, X., Zhu, Y., and Wang, L. (2019). Association between Thalamocortical Functional Connectivity Abnormalities and Cognitive Deficits in Schizophrenia. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-39367-z"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pfaff, D.W. (2013). Neuroscience in the 21st century: From basic to clinical. Neuroscience in the 21st Century: From Basic to Clinical, Springer.","DOI":"10.1007\/978-1-4614-1997-6"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s12311-015-0724-2","article-title":"Consensus Paper: Cerebellar Development","volume":"15","author":"Leto","year":"2016","journal-title":"Cerebellum"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41398-020-01026-7","article-title":"Modulation of cognition and neuronal plasticity in gain- and loss-of-function mouse models of the schizophrenia risk gene Tcf4","volume":"10","author":"Badowska","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103502","DOI":"10.1016\/j.mcn.2020.103502","article-title":"Tcf4 is required for correct brain development during embryogenesis","volume":"106","author":"Mesman","year":"2020","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9882","DOI":"10.1073\/pnas.0701946104","article-title":"Transcription factor Sp4 regulates dendritic patterning during cerebellar maturation","volume":"104","author":"Ramos","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jpsychires.2014.08.006","article-title":"Increased SP4 and SP1 transcription factor expression in the postmortem hippocampus of chronic schizophrenia","volume":"58","author":"Pinacho","year":"2014","journal-title":"J. Psychiatr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1523\/JNEUROSCI.6307-10.2011","article-title":"Differential regulation of dendritic and axonal development by the novel Kr\u00fcppel-like factor dar1","volume":"31","author":"Ye","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hsueh, Y.P., Hirata, Y., Simmen, F.A., Denver, R.J., \u00c1vila-Mendoza, J., and Subramani, A. (2020). Kr\u00fcppel-Like Factors 9 and 13 Block Axon Growth by Transcriptional Repression of Key Components of the cAMP Signaling Pathway. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.602638"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Malt, E.A., Juhasz, K., Malt, U.F., and Naumann, T. (2016). A role for the transcription factor Nk2 homeobox 1 in schizophrenia: Convergent evidence from animal and human studies. Front. Behav. Neurosci., 10.","DOI":"10.3389\/fnbeh.2016.00059"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Vera-Montecinos, A., Rodr\u00edguez-Mias, R., MacDowell, K.S., Garc\u00eda-Bueno, B., Bris, \u00c1.G., Caso, J.R., Vill\u00e9n, J., and Ramos, B. (2021). Analysis of Molecular Networks in the Cerebellum in Chronic Schizophrenia: Modulation by Early Postnatal Life Stressors in Murine Models. Int. J. Mol. Sci., 22.","DOI":"10.1101\/2021.02.21.432145"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1007\/s00702-009-0319-5","article-title":"The interplay between mitochondrial complex I, dopamine and Sp1 in schizophrenia","volume":"116","year":"2009","journal-title":"J Neural. Transm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1192\/bjp.bp.114.152140","article-title":"Specificity proteins 1 and 4, hippocampal volume and first-episode psychosis","volume":"208","author":"Pinacho","year":"2016","journal-title":"Br. J. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1016\/j.jpsychires.2013.07.019","article-title":"Reduced expression of SP1 and SP4 transcription factors in peripheral blood mononuclear cells in first-episode psychosis","volume":"47","author":"Pinacho","year":"2013","journal-title":"J. Psychiatr. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1192\/bjp.bp.114.151688","article-title":"Role played by the SP4 gene in schizophrenia and major depressive disorder in the Han Chinese population","volume":"208","author":"Chen","year":"2016","journal-title":"Br. J. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.jpsychires.2013.03.004","article-title":"Analysis of Sp transcription factors in the postmortem brain of chronic schizophrenia: A pilot study of relationship to negative symptoms","volume":"47","author":"Pinacho","year":"2013","journal-title":"J. Psychiatry Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.euroneuro.2015.05.006","article-title":"Transcription factor SP4 phosphorylation is altered in the postmortem cerebellum of bipolar disorder and schizophrenia subjects","volume":"25","author":"Pinacho","year":"2015","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/jnc.12657","article-title":"Phosphorylation of the transcription factor Sp4 is reduced by NMDA receptor signaling","volume":"129","author":"Saia","year":"2014","journal-title":"J. Neurochem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pinacho, R., Saia, G., Fust\u00e9, M., Mel\u00e9ndez-P\u00e9rez, I., Villalta-Gil, V., Haro, J.M., Gill, G., and Ramos, B. (2015). Phosphorylation of transcription factor specificity protein 4 is increased in peripheral blood mononuclear cells of first-episode psychosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0125115"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s41380-021-01376-8","article-title":"Over-representation of potential SP4 target genes within schizophrenia-risk genes","volume":"27","author":"Zhou","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.psychres.2019.03.044","article-title":"Functional analyses and effect of DNA methylation on the EGR1 gene in patients with schizophrenia","volume":"275","author":"Hu","year":"2019","journal-title":"Psychiatry Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13073-017-0458-5","article-title":"Post-mortem molecular profiling of three psychiatric disorders","volume":"9","author":"Ramaker","year":"2017","journal-title":"Genome Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1007\/s11064-022-03599-9","article-title":"Elevation of EGR1\/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model","volume":"47","author":"Iwakura","year":"2022","journal-title":"Neurochem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1093\/bfgp\/elr036","article-title":"An integrative functional genomics approach for discovering biomarkers in Schizophrenia","volume":"10","author":"Vawter","year":"2011","journal-title":"Brief. Funct. Genom."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Juraeva, D., Haenisch, B., Zapatka, M., Frank, J., GROUP Investigators, PSYCH-GEMS SCZ Working Group, Witt, S.H., M\u00fchleisen, T.W., Treutlein, J., and Strohmaier, J. (2014). Integrated Pathway-Based Approach Identifies Association between Genomic Regions at CTCF and CACNB2 and Schizophrenia. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004345"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41467-019-08666-4","article-title":"Functional genomics reveal gene regulatory mechanisms underlying schizophrenia risk","volume":"10","author":"Huo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1093\/brain\/awab357","article-title":"Regulatory variants at 2q33.1 confer schizophrenia risk by modulating distal gene TYW5 expression","volume":"145","author":"Li","year":"2022","journal-title":"Brain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/schbul\/sbv184","article-title":"Cortical PGC-1\u03b1-Dependent Transcripts Are Reduced in Postmortem Tissue from Patients with Schizophrenia","volume":"42","author":"McMeekin","year":"2016","journal-title":"Schizophr. Bull."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"82","DOI":"10.11648\/j.cnn.20210504.13","article-title":"The NRF1\/miR-4514\/SOCS3 Pathway Is Associated with Schizophrenia Pathogenesis","volume":"5","author":"Liu","year":"2021","journal-title":"Clin. Neurol. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1001\/jamapsychiatry.2017.1986","article-title":"Identification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive function","volume":"74","author":"Smeland","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/mp.2016.254","article-title":"MEF2C transcription factor is associated with the genetic and epigenetic risk architecture of schizophrenia and improves cognition in mice","volume":"23","author":"Mitchell","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1176\/appi.ajp.2014.14010004","article-title":"Lower Expression of Glutamic Acid Decarboxylase 67 in the Prefrontal Cortex in Schizophrenia: Contribution of Altered Regulation by Zif268","volume":"171","author":"Kimoto","year":"2014","journal-title":"Am. J. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1073\/pnas.0610765104","article-title":"Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia","volume":"104","author":"Yamada","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.ygeno.2005.12.011","article-title":"Human KLF17 is a new member of the Sp\/KLF family of transcription factors","volume":"87","author":"Crofts","year":"2006","journal-title":"Genomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/mp.2014.82","article-title":"Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder","volume":"20","author":"Zhao","year":"2015","journal-title":"Mol. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12035-019-01694-7","article-title":"Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis","volume":"57","author":"Hung","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.mcn.2009.06.008","article-title":"Sp4-dependent repression of neurotrophin-3 limits dendritic branching","volume":"42","author":"Ramos","year":"2009","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1128\/MCB.25.13.5699-5711.2005","article-title":"Transcription Factor KLF7 Is Important for Neuronal Morphogenesis in Selected Regions of the Nervous System","volume":"25","author":"Laub","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/dbio.2001.0243","article-title":"Developmental expression of mouse Kr\u00fcppel-like transcription factor KLF7 suggests a potential role in neurogenesis","volume":"233","author":"Laub","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/mp.2013.45","article-title":"The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing","volume":"19","author":"Barry","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000477299","article-title":"The Nuclear Proteome of White and Gray Matter from Schizophrenia Postmortem Brains","volume":"3","author":"Santana","year":"2017","journal-title":"Complex Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"15873","DOI":"10.1073\/pnas.0903413106","article-title":"DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms","volume":"106","author":"Nakata","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/hmg\/ddl449","article-title":"Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia","volume":"16","author":"Law","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1261\/rna.492907","article-title":"Regulation of transcription of the RNA splicing factor hSlu7 by Elk-1 and Sp1 affects alternative splicing","volume":"13","author":"Alberstein","year":"2007","journal-title":"RNA"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1126\/science.1122513","article-title":"A Calcium-Regulated MEF2 Sumoylation Switch Controls Postsynaptic Differentiation","volume":"311","author":"Shalizi","year":"2006","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Lisek, M., Przybyszewski, O., Zylinska, L., Guo, F., and Boczek, T. (2023). The Role of MEF2 Transcription Factor Family in Neuronal Survival and Degeneration. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043120"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.pnpbp.2014.12.009","article-title":"A molecular pathway analysis informs the genetic background at risk for schizophrenia","volume":"59","author":"Crisafulli","year":"2015","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.schres.2015.08.037","article-title":"Linkage and whole genome sequencing identify a locus on 6q25\u201326 for formal thought disorder and implicate MEF2A regulation","volume":"169","author":"Thygesen","year":"2015","journal-title":"Schizophr. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Carmichael, R.E., Wilkinson, K.A., Craig, T.J., Ashby, M.C., and Henley, J.M. (2018). MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc\/Arg3.1. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-23440-0"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.3390\/ijms14047089","article-title":"Roles of Rho GTPases in intracellular transport and cellular transformation","volume":"14","author":"Chi","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/jnc.13077","article-title":"Early growth response 1 (Egr-1) directly regulates GABAA receptor \u03b12, \u03b14, and \u03b8 subunits in the hippocampus","volume":"133","author":"Mo","year":"2015","journal-title":"J. Neurochemistry."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Duclot, F., and Kabbaj, M. (2017). The role of early growth response 1 (EGR1) in brain plasticity and neuropsychiatric disorders. Front. Behav. Neurosci., 11.","DOI":"10.3389\/fnbeh.2017.00035"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.bbamcr.2005.03.003","article-title":"ER-to-Golgi transport: Form and formation of vesicular and tubular carriers","volume":"1744","author":"Watson","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Qin, F., Chen, G., Yu, K.N., Yang, M., Cao, W., Kong, P., Peng, S., Sun, M., Nie, L., and Han, W. (2022). Golgi Phosphoprotein 3 Mediates Radiation-Induced Bystander Effect via ERK\/EGR1\/TNF-\u03b1 Signal Axis. Antioxidants, 11.","DOI":"10.3390\/antiox11112172"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Etemadik, M., Nia, A., Wetter, L., and Feuk, L. (2020). Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-57467-z"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.pnpbp.2012.08.015","article-title":"Neurodevelopment and inflammatory patterns in schizophrenia in relation to pathophysiology","volume":"42","author":"Altamura","year":"2013","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.biopsych.2009.06.005","article-title":"Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness Study","volume":"66","author":"Meyer","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.schres.2022.03.004","article-title":"Neurodegenerative model of schizophrenia: Growing evidence to support a revisit","volume":"243","author":"Stone","year":"2022","journal-title":"Schizophr. Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Comer, A.L., Carrier, M., Tremblay, M.\u00c8., and Cruz-Mart\u00edn, A. (2020). The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00274"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/jnen\/nlae066","article-title":"Increased inflammasome protein expression identified in microglia from postmortem brains with schizophrenia","volume":"83","author":"Gober","year":"2024","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1176\/appi.focus.20200015","article-title":"Evaluating the Hypothesis That Schizophrenia Is an Inflammatory Disorder","volume":"18","author":"Miller","year":"2020","journal-title":"Focus"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e1024","DOI":"10.1038\/tp.2016.278","article-title":"Inflammation and the neural diathesis-stress hypothesis of schizophrenia: A reconceptualization","volume":"7","author":"Howes","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100038","DOI":"10.1016\/j.bbih.2020.100038","article-title":"Overlapping evidence of innate immune dysfunction in psychotic and affective disorders","volume":"2","author":"Hughes","year":"2020","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Fond, G., Lan\u00e7on, C., Korchia, T., Auquier, P., and Boyer, L. (2020). The Role of Inflammation in the Treatment of Schizophrenia. Front. Psychiatry, 11.","DOI":"10.3389\/fpsyt.2020.00160"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Carril Pardo, C., Oyarce Merino, K., and Vera-Montecinos, A. (2025). Neuroinflammatory Loop in Schizophrenia, Is There a Relationship with Symptoms or Cognition Decline?. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010310"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Cui, L.-B., Wang, X.-Y., Fu, Y.-F., Liu, X.-F., Wei, Y., Zhao, S.-W., Gu, Y.-W., Fan, J.-W., Wu, W.-J., and Gong, H. (2023). Transcriptional level of inflammation markers associates with short-term brain structural changes in first-episode schizophrenia. BMC Med., 21.","DOI":"10.1186\/s12916-023-02963-y"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"109130","DOI":"10.1016\/j.intimp.2022.109130","article-title":"Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach","volume":"111","author":"Aliyu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e23033","DOI":"10.1096\/fj.202300005R","article-title":"KLF7 promotes adipocyte inflammation and glucose metabolism disorder by activating the PKC\u03b6\/NF-\u03baB pathway","volume":"37","author":"Yang","year":"2023","journal-title":"FASEB J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1756494","DOI":"10.1155\/2018\/1756494","article-title":"The effect and mechanism of KLF7 in the TLR4\/NF-\u03baB\/IL-6 inflammatory signal pathway of adipocytes","volume":"2018","author":"Zhang","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.mcn.2018.07.001","article-title":"Regulation of actin dynamics during structural plasticity of dendritic spines: Signaling messengers and actin-binding proteins","volume":"91","author":"Borovac","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"155441","DOI":"10.1016\/j.cyto.2021.155441","article-title":"Serum interleukin-6 in schizophrenia: A system review and meta-analysis","volume":"141","author":"Zhou","year":"2021","journal-title":"Cytokine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1016\/j.ajpath.2013.01.029","article-title":"Kruppel-like factor 2 is a transcriptional regulator of chronic and acute inflammation","volume":"182","author":"Nayak","year":"2013","journal-title":"Am. J. Pathol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/cmi.2014.125","article-title":"Kr\u00fcppel-like factor 4 negatively regulates cellular antiviral immune response","volume":"13","author":"Luo","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"10318","DOI":"10.1074\/jbc.M113.526749","article-title":"Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization","volume":"289","author":"Date","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"9741","DOI":"10.1128\/MCB.25.22.9741-9752.2005","article-title":"Interleukin-21 Receptor Gene Induction in Human T Cells Is Mediated by T-Cell Receptor-Induced Sp1 Activity","volume":"25","author":"Wu","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5998","DOI":"10.1002\/jcp.27151","article-title":"MiR302c, Sp1, and NFATc2 regulate interleukin-21 expression in human CD4+CD45RO+ T lymphocytes","volume":"234","author":"Aoun","year":"2019","journal-title":"J. Cell. Physiology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"156437","DOI":"10.1016\/j.cyto.2023.156437","article-title":"The role of Interleukin-21 in autoimmune Diseases: Mechanisms, therapeutic Implications, and future directions","volume":"173","author":"Shbeer","year":"2024","journal-title":"Cytokine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1745-7270.2006.00147.x","article-title":"Transcription factors Ets2 and Sp1 act synergistically with histone acetyltransferase p300 in activating human interleukin-12 p40 promoter","volume":"38","author":"Sun","year":"2006","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Powell, M.D., Read, K.A., Sreekumar, B.K., Jones, D.M., and Oestreich, K.J. (2019). IL-12 signaling drives the differentiation and function of a TH1-derived TFH1-like cell population. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-50614-1"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/sj.mp.4001084","article-title":"The plasma levels of interleukin-12 in schizophrenia, major depression, and bipolar mania: Effects of psychotropic drugs","volume":"7","author":"Kim","year":"2002","journal-title":"Mol. Psychiatry"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1440-1819.2008.01798.x","article-title":"The value of interleukin-12B (p40) gene promoter polymorphism in patients with schizophrenia in a region of East Turkey","volume":"62","author":"Ozbey","year":"2008","journal-title":"Psychiatry Clin. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s00018-004-4399-y","article-title":"Sp1-associated activation of macrophage inflammatory protein-2 promoter by CpG-oligodeoxynucleotide and lipopolysaccharide","volume":"62","author":"Lee","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Iwanaszko, M., and Kimmel, M. (2015). NF-\u03baB and IRF pathways: Cross-regulation on target genes promoter level. BMC Genom., 16.","DOI":"10.1186\/s12864-015-1511-7"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.pnpbp.2017.08.005","article-title":"Differential regulation of the TLR4 signalling pathway in post-mortem prefrontal cortex and cerebellum in chronic schizophrenia: Relationship with SP transcription factors","volume":"79","author":"MacDowell","year":"2017","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1001\/archpsyc.1995.03950190026004","article-title":"Increased Rate of P300 Latency Prolongation with Age in Schizophrenia: Electrophysiological Evidence for a Neurodegenerative Process","volume":"52","author":"Faux","year":"1995","journal-title":"Arch Gen Psychiatry"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Mor\u00e9n, C., Treder, N., Mart\u00ednez-Pinte\u00f1o, A., Rodr\u00edguez, N., Arbelo, N., Madero, S., G\u00f3mez, M., Mas, S., Gass\u00f3, P., and Parellada, E. (2022). Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia. Antioxidants, 11.","DOI":"10.3390\/antiox11112275"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.schres.2005.08.014","article-title":"Apoptotic mechanisms and the synaptic pathology of schizophrenia","volume":"81","author":"Glantz","year":"2005","journal-title":"Schizophr. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41398-021-01385-9","article-title":"Glutamate and microglia activation as a driver of dendritic apoptosis: A core pathophysiological mechanism to understand schizophrenia","volume":"11","author":"Parellada","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7096","DOI":"10.1038\/sj.onc.1209696","article-title":"Overexpression of Sp1 transcription factor induces apoptosis","volume":"25","author":"Deniaud","year":"2006","journal-title":"Oncogene"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10495-017-1437-4","article-title":"Caspase cleavage of transcription factor Sp1 enhances apoptosis","volume":"23","author":"Torabi","year":"2018","journal-title":"Apoptosis"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Deniaud, E., Baguet, J., Chalard, R., Blanquier, B., Brinza, L., Meunier, J., Michallet, M.-C., Laugraud, A., Ah-Soon, C., and Wierinckx, A. (2009). Overexpression of Transcription Factor Sp1 Leads to Gene Expression Perturbations and Cell Cycle Inhibition. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007035"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1101\/gad.1227705","article-title":"The zinc finger transcription factor Klf7 is required for TrkA gene expression and development of nociceptive sensory neurons","volume":"19","author":"Lei","year":"2005","journal-title":"Genes Dev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1172\/JCI77084","article-title":"Kr\u00fcppel-like factor 6 regulates mitochondrial function in the kidney","volume":"125","author":"Mallipattu","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e2024414118","DOI":"10.1073\/pnas.2024414118","article-title":"Kr\u00fcppel-like factor 6\u2013mediated loss of BCAA catabolism contributes to kidney injury in mice and humans","volume":"118","author":"Piret","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1080\/01616412.2024.2376999","article-title":"USP7 alleviates neuronal inflammation and apoptosis in spinal cord injury via deubiquitinating NRF1\/KLF7 axis","volume":"46","author":"Xu","year":"2024","journal-title":"Neurol. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1016\/j.pnpbp.2005.03.010","article-title":"Apoptotic mechanisms in the pathophysiology of schizophrenia","volume":"29","author":"Jarskog","year":"2005","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0006-3223(00)01058-1","article-title":"Antipsychotic treatment induces alterations in dendrite- and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex","volume":"49","author":"Lidow","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"W77","DOI":"10.1093\/nar\/gkt439","article-title":"WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): Update 2013","volume":"41","author":"Wang","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1176\/appi.ajp.2009.09060802","article-title":"International consensus study of antipsychotic dosing","volume":"167","author":"Gardner","year":"2010","journal-title":"Am. J. Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:13:17Z","timestamp":1760029997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,12]]},"references-count":107,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083653"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083653","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,4,12]]}}}