{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:12:43Z","timestamp":1760058763696,"version":"build-2065373602"},"reference-count":113,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Research Council of T\u00fcrkiye","award":["TUBITAK 119Z389","TUSEB 28520"],"award-info":[{"award-number":["TUBITAK 119Z389","TUSEB 28520"]}]},{"name":"Health Institutes of T\u00fcrkiye","award":["TUBITAK 119Z389","TUSEB 28520"],"award-info":[{"award-number":["TUBITAK 119Z389","TUSEB 28520"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Background\/Objectives: X-inactive-specific transcript (XIST) is a factor that plays a role in neuroinflammation. This study investigated the role of XIST in neuronal development, neuroinflammation, myelination, and therapeutic responses within cerebral organoids in the context of Multiple Sclerosis (MS) pathogenesis. Methods: Human cerebral organoids with oligodendrocytes were produced from XIST-silenced H9 cells, and the mature organoids were subsequently treated with either FTY720 or DMF. Gene expression related to inflammation and myelination was subsequently analyzed via qRT-PCR. Immunofluorescence staining was used to assess the expression of proteins related to inflammation, myelination, and neuronal differentiation. Alpha-synuclein protein levels were also checked via ELISA. Finally, transcriptome analysis was conducted on the organoid samples. Results: XIST-silenced organoids presented a 2-fold increase in the expression of neuronal stem cells, excitatory neurons, microglia, and mature oligodendrocyte markers. In addition, XIST silencing increased IL-10 mRNA expression by 2-fold and MBP and PLP1 expression by 2.3- and 0.6-fold, respectively. Although XIST silencing tripled IBA1 protein expression, it did not affect organoid MBP expression. FTY720, but not DMF, distinguished MBP and IBA1 expression in XIST-silenced organoids. Furthermore, XIST silencing reduced the concentration of alpha-synuclein from 300 to 100 pg\/mL, confirming its anti-inflammatory role. Transcriptomic and gene enrichment analyses revealed that the differentially expressed genes are involved in neural development and immune processes, suggesting the role of XIST in neuroinflammation. The silencing of XIST modified the expression of genes associated with inflammation, myelination, and neuronal growth in cerebral organoids, indicating a potential involvement in the pathogenesis of MS. Conclusions: XIST may contribute to the MS pathogenesis as well as neuroinflammatory diseases such as and Alzheimer\u2019s and Parkinson\u2019s diseases and may be a promising therapeutic target.<\/jats:p>","DOI":"10.3390\/ncrna11030031","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Long Non-Coding RNA X-Inactive-Specific Transcript (XIST) in Neuroinflammation and Myelination: Insights from Cerebral Organoids and Implications for Multiple Sclerosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Nihan","family":"Aktas Pepe","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri 38080, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4772-2698","authenticated-orcid":false,"given":"Busra","family":"Acar","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri 38080, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gozde","family":"Erturk Zararsiz","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Faculty of Medicine, Erciyes University, Kayseri 38039, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-0961","authenticated-orcid":false,"given":"Serife","family":"Ayaz Guner","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty Sciences, Izmir Institute of Technology, Izmir 35430, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8444-376X","authenticated-orcid":false,"given":"Alaattin","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri 38080, T\u00fcrkiye"},{"name":"Department of Biology, Faculty of Sciences, Pamukkale University, Kinikli, Denizli 20070, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/0092-8674(92)90520-M","article-title":"The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus","volume":"71","author":"Brown","year":"1992","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nsmb.3370","article-title":"Novel players in X inactivation: Insights into Xist-mediated gene silencing and chromosome conformation","volume":"24","author":"Heard","year":"2017","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1016\/j.gendis.2022.04.007","article-title":"Long noncoding RNA XIST: Mechanisms for X chromosome inactivation, roles in sex-biased diseases, and therapeutic opportunities","volume":"9","author":"Li","year":"2022","journal-title":"Genes Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, W., Min, L., Qiu, X., Wu, X., Liu, C., Ma, J., Zhang, D., and Zhu, L. (2021). Biological Function of Long Non-coding RNA (LncRNA) Xist. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645647"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Siniscalchi, C., Di Palo, A., Russo, A., and Potenza, N. (2022). The lncRNAs at X Chromosome Inactivation Center: Not Just a Matter of Sex Dosage Compensation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23020611"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6032","DOI":"10.1002\/jcp.29530","article-title":"Activation of CB2R with AM1241 ameliorates neurodegeneration via the Xist\/miR-133b-3p\/Pitx3 axis","volume":"235","author":"He","year":"2020","journal-title":"J. Cell Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/cbin.11263","article-title":"Silencing of long noncoding RNA XIST attenuated Alzheimer\u2019s disease-related BACE1 alteration through miR-124","volume":"44","author":"Yue","year":"2020","journal-title":"Cell Biol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.18632\/aging.202378","article-title":"LncRNA XIST sponges miR-199a-3p to modulate the Sp1\/LRRK2 signal pathway to accelerate Parkinson\u2019s disease progression","volume":"13","author":"Zhou","year":"2021","journal-title":"Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"134649","DOI":"10.1016\/j.neulet.2019.134649","article-title":"Knockdown of long noncoding RNA XIST mitigates the apoptosis and inflammatory injury of microglia cells after spinal cord injury through miR-27a\/Smurf1 axis","volume":"715","author":"Zhao","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1159\/000523781","article-title":"LncRNA XIST Engages in Psoriasis via Sponging miR-338-5p to Regulate Keratinocyte Proliferation and Inflammation","volume":"35","author":"Wang","year":"2022","journal-title":"Skin. Pharmacol. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Cohen, J., Mathew, A., Dourvetakis, K.D., Sanchez-Guerrero, E., Pangeni, R.P., Gurusamy, N., Aenlle, K.K., Ravindran, G., Twahir, A., and Isler, D. (2024). Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders. Cells, 13.","DOI":"10.3390\/cells13060511"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"D\u2019Anca, M., Buccellato, F.R., Tartaglia, G.M., Del Fabbro, M., Muti, P., Scarpini, E., Galimberti, D., and Ghezzi, L. (2023). Why Is Multiple Sclerosis More Frequent in Women? Role of the Immune System and of Oral and Gut Microbiota. Appl. Sci., 13.","DOI":"10.3390\/app13105881"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nytrova, P., and Dolezal, O. (2022). Sex bias in multiple sclerosis and neuromyelitis optica spectrum disorders: How it influences clinical course, MRI parameters and prognosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.933415"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103859","DOI":"10.1016\/j.mcn.2023.103859","article-title":"Sex differences in susceptibility to substance use disorder: Role for X chromosome inactivation and escape?","volume":"125","author":"Krueger","year":"2023","journal-title":"Mol. Cell Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s10020-020-00256-1","article-title":"Escape from X chromosome inactivation and female bias of autoimmune diseases","volume":"26","author":"Mousavi","year":"2020","journal-title":"Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ngwa, C., Misrani, A., Manyam, K.V., Xu, Y., Qi, S., Sharmeen, R., McCullough, L., and Liu, F. (2024). Escape of Kdm6a from X chromosome is detrimental to ischemic brains via IRF5 signaling. Res. Sq., preprint.","DOI":"10.21203\/rs.3.rs-4986866\/v1"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cipriano, G.L., Schepici, G., Mazzon, E., and Anchesi, I. (2024). Multiple Sclerosis: Roles of miRNA, lcnRNA, and circRNA and Their Implications in Cellular Pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042255"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jalaiei, A., Asadi, M.R., Sabaie, H., Dehghani, H., Gharesouran, J., Hussen, B.M., Taheri, M., Ghafouri-Fard, S., and Rezazadeh, M. (2021). Long Non-Coding RNAs, Novel Offenders or Guardians in Multiple Sclerosis: A Scoping Review. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.774002"},{"key":"ref_20","first-page":"3915","article-title":"LncRNA XIST knockdown attenuates A\u03b2(25-35)-induced toxicity, oxidative stress, and apoptosis in primary cultured rat hippocampal neurons by targeting miR-132","volume":"11","author":"Wang","year":"2018","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/01677063.2022.2028784","article-title":"lncRNA XIST induces A\u03b2 accumulation and neuroinflammation by the epigenetic repression of NEP in Alzheimer\u2019s disease","volume":"36","author":"Yan","year":"2022","journal-title":"J. Neurogenet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Andrade, F. (2024). Opinion: How does XIST promote sex bias in autoimmune diseases?. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1399408"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e17852","DOI":"10.1016\/j.heliyon.2023.e17852","article-title":"lncRNA XIST inhibition promotes M2 polarization of microglial and aggravates the spinal cord injury via regulating miR-124-3p\/IRF1 axis","volume":"9","author":"Yang","year":"2023","journal-title":"Heliyon"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1124\/molpharm.122.000530","article-title":"The Common LncRNAs of Neuroinflammation-Related Diseases","volume":"103","author":"Zeng","year":"2023","journal-title":"Mol. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00438-020-01750-1","article-title":"Identification of hub lncRNA ceRNAs in multiple sclerosis based on ceRNA mechanisms","volume":"296","author":"Ding","year":"2021","journal-title":"Mol. Genet. Genom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102826","DOI":"10.1016\/j.autrev.2021.102826","article-title":"Disease modifying therapies in relapsing-remitting multiple sclerosis: A systematic review and network meta-analysis","volume":"20","author":"Liu","year":"2021","journal-title":"Autoimmun. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ferret-Sena, V., Capela, C., Macedo, A., Salgado, A.V., Derudas, B., Staels, B., and Sena, A. (2022). Fingolimod treatment modulates PPARgamma and CD36 gene expression in women with multiple sclerosis. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.1077381"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s40263-021-00798-w","article-title":"Sphingosine 1-Phosphate Receptor Modulators for Multiple Sclerosis","volume":"35","author":"Roy","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1089\/ars.2015.6622","article-title":"Pharmacodynamics of Dimethyl Fumarate Are Tissue Specific and Involve NRF2-Dependent and -Independent Mechanisms","volume":"24","author":"Brennan","year":"2016","journal-title":"Antioxid. Redox Signal"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2205042119","DOI":"10.1073\/pnas.2205042119","article-title":"High-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis","volume":"119","author":"Diebold","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e183","DOI":"10.1212\/NXI.0000000000000183","article-title":"Dimethyl fumarate treatment alters circulating T helper cell subsets in multiple sclerosis","volume":"3","author":"Gross","year":"2016","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105126","DOI":"10.1016\/j.msard.2023.105126","article-title":"Dimethyl fumarate treatment in relapsing remitting MS changes the inflammatory CSF protein profile by a prominent decrease in T-helper 1 immunity","volume":"80","author":"Hojjati","year":"2023","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.4049\/jimmunol.1601532","article-title":"Dimethyl Fumarate Selectively Reduces Memory T Cells and Shifts the Balance between Th1\/Th17 and Th2 in Multiple Sclerosis Patients","volume":"198","author":"Wu","year":"2017","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1038\/nprot.2014.158","article-title":"Generation of cerebral organoids from human pluripotent stem cells","volume":"9","author":"Lancaster","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_35","unstructured":"Acar, B., Aktas-Pepe, N., and Sen, A. (2021). Optimization of myelination on human cerebral organoids for studying multiple sclerosis (MS). EuroBiotech J., 5."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1002\/stem.3373","article-title":"Sox2 controls neural stem cell self-renewal through a Fos-centered gene regulatory network","volume":"39","author":"Pagin","year":"2021","journal-title":"Stem Cells"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e126751","DOI":"10.1172\/jci.insight.126751","article-title":"Altered X-chromosome inactivation in T cells may promote sex-biased autoimmune diseases","volume":"4","author":"Syrett","year":"2019","journal-title":"JCI Insight"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Boziki, M., Theotokis, P., Kesidou, E., Karafoulidou, E., Konstantinou, C., Michailidou, I., Bahar, Y., Altintas, A., and Grigoriadis, N. (2022). Sex, aging and immunity in multiple sclerosis and experimental autoimmune encephalomyelitis: An intriguing interaction. Front. Neurol., 13.","DOI":"10.3389\/fneur.2022.1104552"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kingwell, E., Marriott, J.J., Jett\u00e9, N., Pringsheim, T., Makhani, N., Morrow, S.A., Fisk, J.D., Evans, C., B\u00e9land, S.G., and Kulaga, S. (2013). Incidence and prevalence of multiple sclerosis in Europe: A systematic review. BMC Neurol., 13.","DOI":"10.1186\/1471-2377-13-128"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Angeloni, B., Bigi, R., Bellucci, G., Mechelli, R., Ballerini, C., Romano, C., Morena, E., Pellicciari, G., Renie, R., and Rinaldi, V. (2021). A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073696"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1391807","DOI":"10.1155\/2022\/1391807","article-title":"X-Chromosome Inactivation and Related Diseases","volume":"2022","author":"Sun","year":"2022","journal-title":"Genet. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s00439-024-02651-8","article-title":"Trisomy silencing by XIST: Translational prospects and challenges","volume":"143","author":"Gupta","year":"2024","journal-title":"Hum. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101927","DOI":"10.1016\/j.gde.2022.101927","article-title":"A lifelong duty: How Xist maintains the inactive X chromosome","volume":"75","author":"Jacobson","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"929042","DOI":"10.4061\/2011\/929042","article-title":"Knockdown of BACE1-AS Nonprotein-Coding Transcript Modulates Beta-Amyloid-Related Hippocampal Neurogenesis","volume":"2011","author":"Modarresi","year":"2011","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s11062-023-09933-3","article-title":"High Expression of LncRNA XIST as an Index Helping to Diagnose Parkinson\u2019s Disease","volume":"54","author":"Zhang","year":"2022","journal-title":"Neurophysiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12943-021-01472-x","article-title":"Dual CRISPR interference and activation for targeted reactivation of X-linked endogenous FOXP3 in human breast cancer cells","volume":"21","author":"Cui","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.stem.2012.03.008","article-title":"Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes","volume":"11","author":"Anguera","year":"2012","journal-title":"Cell Stem Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1073\/pnas.1917203117","article-title":"Widespread organ tolerance to Xist loss and X reactivation except under chronic stress in the gut","volume":"117","author":"Yang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1016\/j.cell.2022.04.034","article-title":"XIST loss impairs mammary stem cell differentiation and increases tumorigenicity through Mediator hyperactivation","volume":"185","author":"Richart","year":"2022","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/s41592-018-0081-4","article-title":"Induction of myelinating oligodendrocytes in human cortical spheroids","volume":"15","author":"Madhavan","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1002\/bab.2602","article-title":"The inhibitory impact of Schisandrin on inflammation and oxidative stress alleviates LPS-induced acute kidney injury","volume":"71","author":"Liu","year":"2024","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13229-020-00360-3","article-title":"Cerebral organoids as tools to identify the developmental roots of autism","volume":"11","author":"Chan","year":"2020","journal-title":"Mol. Autism"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Espino-Paisan, L., Agudo-Jimenez, T., Rosales-Martinez, I., Lopez-Cotarelo, P., Garcia-Martinez, M.A., Dominguez-Mozo, M.I., Perez-Perez, S., Dieli-Crimi, R., Comabella, M., and Urcelay, E. (2020). A Polymorphism Within the MBP Gene Is Associated With a Higher Relapse Number in Male Patients of Multiple Sclerosis. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00771"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/ana.10425","article-title":"Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis","volume":"53","author":"Zang","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"32609","DOI":"10.1074\/jbc.M500299200","article-title":"Myelin basic protein-primed T cells of female but not male mice induce nitric-oxide synthase and proinflammatory cytokines in microglia: Implications for gender bias in multiple sclerosis","volume":"280","author":"Dasgupta","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00018-020-03500-3","article-title":"Xist attenuates acute inflammatory response by female cells","volume":"78","author":"Shenoda","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1038\/s41388-023-02652-3","article-title":"LncRNA XIST regulates breast cancer stem cells by activating proinflammatory IL-6\/STAT3 signaling","volume":"42","author":"Ma","year":"2023","journal-title":"Oncogene"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s00415-020-10226-6","article-title":"Comparative analysis of dimethyl fumarate and fingolimod in relapsing-remitting multiple sclerosis","volume":"268","author":"Lorscheider","year":"2021","journal-title":"J. Neurol."},{"key":"ref_60","first-page":"86","article-title":"Assessment of fingolimod versus dimethyl fumarate for the treatment of multiple sclerosis; a 24-month follow-up study","volume":"10","author":"Masjedi","year":"2021","journal-title":"Am. J. Clin. Exp. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.1212\/WNL.0000000000005772","article-title":"Fingolimod vs dimethyl fumarate in multiple sclerosis: A real-world propensity score-matched study","volume":"91","author":"Prosperini","year":"2018","journal-title":"Neurology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1001\/jamaneurol.2023.1542","article-title":"Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation","volume":"80","author":"Zhu","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1002\/eji.202149757","article-title":"Multiple sclerosis: Immunopathological heterogeneity and its implications","volume":"52","author":"Engelhardt","year":"2022","journal-title":"Eur. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Guerrero, B.L., and Sicotte, N.L. (2020). Microglia in Multiple Sclerosis: Friend or Foe?. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00374"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Jurga, A.M., Paleczna, M., Kadluczka, J., and Kuter, K.Z. (2021). Beyond the GFAP-Astrocyte Protein Markers in the Brain. Biomolecules, 11.","DOI":"10.3390\/biom11091361"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Arcuri, C., Mecca, C., Bianchi, R., Giambanco, I., and Donato, R. (2017). The Pathophysiological Role of Microglia in Dynamic Surveillance, Phagocytosis and Structural Remodeling of the Developing CNS. Front. Mol. Neurosci., 10.","DOI":"10.3389\/fnmol.2017.00191"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Qin, J., Ma, Z., Chen, X., and Shu, S. (2023). Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1103416"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fleiss, B., Van Steenwinckel, J., Bokobza, C., Shearer, I.K., Ross-Munro, E., and Gressens, P. (2021). Microglia-Mediated Neurodegeneration in Perinatal Brain Injuries. Biomolecules, 11.","DOI":"10.3390\/biom11010099"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"705","DOI":"10.4103\/1673-5374.322423","article-title":"Microglia regulation of synaptic plasticity and learning and memory","volume":"17","author":"Cornell","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lee, Y.S., Gupta, D.P., Park, S.H., Yang, H.J., and Song, G.J. (2021). Anti-Inflammatory Effects of Dimethyl Fumarate in Microglia via an Autophagy Dependent Pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.612981"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13041-023-01047-5","article-title":"Ameliorative effects of Fingolimod (FTY720) on microglial activation and psychosis-related behavior in short term cuprizone exposed mice","volume":"16","author":"Li","year":"2023","journal-title":"Mol. Brain"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"577432","DOI":"10.1016\/j.jneuroim.2020.577432","article-title":"Low serum Alpha-SYNUCLEIN and oligomer Alpha-SYNUCLEIN levels in multiple sclerosis patients","volume":"350","author":"Bilge","year":"2020","journal-title":"J. Neuroimmunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1093\/brain\/awy151","article-title":"The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells","volume":"141","author":"Saji","year":"2018","journal-title":"Brain"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12974-016-0694-4","article-title":"alpha-Synuclein deficiency promotes neuroinflammation by increasing Th1 cell-mediated immune responses","volume":"13","author":"Ettle","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jns.2018.11.003","article-title":"Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: A pilot cross-sectional study","volume":"396","author":"Mejia","year":"2019","journal-title":"J. Neurol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100352","DOI":"10.1016\/j.crmeth.2022.100352","article-title":"De-erosion of X chromosome dosage compensation by the editing of XIST regulatory regions restores the differentiation potential in hPSCs","volume":"2","author":"Motosugi","year":"2022","journal-title":"Cell Rep. Methods"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.devcel.2019.12.015","article-title":"Silencing Trisomy 21 with XIST in Neural Stem Cells Promotes Neuronal Differentiation","volume":"52","author":"Czerminski","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Azzolini, F., Gilio, L., Pavone, L., Iezzi, E., Dolcetti, E., Bruno, A., Buttari, F., Musella, A., Mandolesi, G., and Guadalupi, L. (2022). Neuroinflammation Is Associated with GFAP and sTREM2 Levels in Multiple Sclerosis. Biomolecules, 12.","DOI":"10.3390\/biom12020222"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4142\/jvs.2014.15.1.35","article-title":"Immunohistochemical evaluation of the goat forestomach during prenatal development","volume":"15","author":"Garcia","year":"2014","journal-title":"J. Vet. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.apjtm.2017.10.027","article-title":"Expression of vimentin and glial fibrillary acidic protein in central nervous system development of rats","volume":"10","author":"Luo","year":"2017","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"40638","DOI":"10.1074\/jbc.M111.271320","article-title":"Microtubule-associated protein 1B (MAP1B) is required for dendritic spine development and synaptic maturation","volume":"286","author":"Tortosa","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Baba, Y., Onishi-Sakamoto, S., Ide, K., and Nishifuji, K. (2022). Nestin is a marker of unipotent embryonic and adult progenitors differentiating into an epithelial cell lineage of the hair follicles. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-22427-2"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Du, Y., Bradshaw, W.J., Leisner, T.M., Annor-Gyamfi, J.K., Qian, K., Bashore, F.M., Sikdar, A., Nwogbo, F.O., Ivanov, A.A., and Frye, S.V. (2023). Discovery of FERM domain protein\u2013protein interaction inhibitors for MSN and CD44 as a potential therapeutic approach for Alzheimer\u2019s disease. J. Biol. Chem., 299.","DOI":"10.1101\/2023.05.22.541727"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13024-020-00377-5","article-title":"Flow-cytometric microglial sorting coupled with quantitative proteomics identifies moesin as a highly-abundant microglial protein with relevance to Alzheimer\u2019s disease","volume":"15","author":"Rayaprolu","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1111\/febs.15716","article-title":"The role of PARP1 in neurodegenerative diseases and aging","volume":"289","author":"Mao","year":"2022","journal-title":"FEBS J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/2051-5960-2-38","article-title":"Golgi fragmentation precedes neuromuscular denervation and is associated with endosome abnormalities in SOD1-ALS mouse motor neurons","volume":"2","author":"Kuijpers","year":"2014","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13024-024-00704-0","article-title":"Collagen in the central nervous system: Contributions to neurodegeneration and promise as a therapeutic target","volume":"19","author":"Wareham","year":"2024","journal-title":"Mol. Neurodegener."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.18632\/aging.100924","article-title":"Lack of collagen VI promotes neurodegeneration by impairing autophagy and inducing apoptosis during aging","volume":"8","author":"Cescon","year":"2016","journal-title":"Aging"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Chapman, M.A., and Sorg, B.A. (2024). A Systematic Review of Extracellular Matrix-Related Alterations in Parkinson\u2019s Disease. Brain Sci., 14.","DOI":"10.3390\/brainsci14060522"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/j.1750-3639.2010.00399.x","article-title":"Extracellular matrix in multiple sclerosis lesions: Fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells","volume":"20","author":"Mohan","year":"2010","journal-title":"Brain Pathol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00401-017-1697-7","article-title":"Axonal transport deficits in multiple sclerosis: Spiraling into the abyss","volume":"134","author":"Hoogenraad","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Misrielal, C., Mauthe, M., Reggiori, F., and Eggen, B.J.L. (2020). Autophagy in Multiple Sclerosis: Two Sides of the Same Coin. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.603710"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Delic, S., Miletic Drakulic, S., Stepovic, M., Milosavljevic, J., Kovacevic Dimitrijevic, M., Jovanovic, K., Marinkovic, I., Tepavcevic, M., Janicijevic, N., and Mitrovic, A. (2025). The Connection Between Oxidative Stress, Mitochondrial Dysfunction, Iron Metabolism and Microglia in Multiple Sclerosis: A Narrative Review. NeuroSci, 6.","DOI":"10.3390\/neurosci6010023"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.15252\/embr.201643668","article-title":"LncRNA GAS5 inhibits microglial M2 polarization and exacerbates demyelination","volume":"18","author":"Sun","year":"2017","journal-title":"EMBO Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.jneuroim.2018.11.013","article-title":"Malat1 long noncoding RNA regulates inflammation and leukocyte differentiation in experimental autoimmune encephalomyelitis","volume":"328","author":"Masoumi","year":"2019","journal-title":"J. Neuroimmunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.msard.2018.07.044","article-title":"Dysregulation of long non-coding RNA profile in peripheral blood of multiple sclerosis patients","volume":"25","author":"Dastmalchi","year":"2018","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jneuroim.2018.08.008","article-title":"LncRNAs expression profile in peripheral blood mononuclear cells from multiple sclerosis patients","volume":"324","author":"Fenoglio","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Shihan, M.H., Novo, S.G., Le Marchand, S.J., Wang, Y., and Duncan, M.K. (2021). A simple method for quantitating confocal fluorescent images. Biochem. Biophys. Rep., 25.","DOI":"10.1016\/j.bbrep.2021.100916"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1074\/mcp.TIR117.000516","article-title":"Stable Isotope Dynamic Labeling of Secretomes (SIDLS) Identifies Authentic Secretory Proteins Released by Cancer and Stromal Cells","volume":"17","author":"Hammond","year":"2018","journal-title":"Mol. Cell. Proteom."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s10875-024-01777-8","article-title":"DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans","volume":"44","author":"Azizoglu","year":"2024","journal-title":"J. Clin. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1038\/nprot.2016.136","article-title":"The MaxQuant computational platform for mass spectrometry-based shotgun proteomics","volume":"11","author":"Tyanova","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_102","unstructured":"Andrews, S. (2010). FastQC: A Quality Control Tool for High Throughput Sequence Data, Babraham Institute. CB22 3AT 2010."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: Transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000Research"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/bioinformatics\/btt087","article-title":"EBSeq: An empirical Bayes hierarchical model for inference in RNA-seq experiments","volume":"29","author":"Leng","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Law, C.W., Chen, Y., Shi, W., and Smyth, G.K. (2014). voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol., 15.","DOI":"10.1186\/gb-2014-15-2-r29"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Dennis, G., Sherman, B.T., Hosack, D.A., Yang, J., Gao, W., Lane, H.C., and Lempicki, R.A. (2003). DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol., 4.","DOI":"10.1186\/gb-2003-4-5-p3"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"}],"container-title":["Non-Coding RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-553X\/11\/3\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:23:54Z","timestamp":1760030634000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-553X\/11\/3\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":113,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ncrna11030031"],"URL":"https:\/\/doi.org\/10.3390\/ncrna11030031","relation":{},"ISSN":["2311-553X"],"issn-type":[{"type":"electronic","value":"2311-553X"}],"subject":[],"published":{"date-parts":[[2025,4,29]]}}}