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Several diseases collectively named tauopathies, such as Alzheimer\u2019s disease, have been associated with an imbalance in the expression of alternative spliced Tau transcripts and the accumulation of hyperphosphorylated Tau, causing dysfunction and death of neuronal cells. Therefore, understanding the Tau exon splicing mechanisms may contribute to elucidating molecular factors that could underlie the development of neurodegenerative disorders. The aim of this study was to define the role of selected splicing factors in regulating Tau exon expression in cell lines and neuronal organoids. We demonstrated the role of the RNA-binding motif protein 20 (RBM20) splicing factor in regulating Tau exon 6 and exon 10, applying RNA-binding assay and qPCR analyses. Furthermore, we demonstrated that Tau expression was regulated during cerebral organoid differentiation, recapitulating in vivo Tau expression. These results suggest the feasibility of using brain organoid technology to study Tau alternative splicing during neural development, confirming that 3D cellular models could be used to study and characterize pathological processes taking place in Tau-related pathologies.<\/jats:p>","DOI":"10.3390\/ijms27094001","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T08:03:47Z","timestamp":1777536227000},"page":"4001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of Tau Alternative Splicing: A Novel Role for the Ribonucleoprotein RBM20"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7482-3251","authenticated-orcid":false,"given":"Andrea","family":"Corsi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8486-2809","authenticated-orcid":false,"given":"Angela","family":"Valentino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5018-4311","authenticated-orcid":false,"given":"Maria Giusy","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1430-3638","authenticated-orcid":false,"given":"Giacomo","family":"Menichetti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Belpinati","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta P.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular, Instituto Universitario de Biolog\u00eda Molecular (IUBM) and Centro de Biolog\u00eda Molecular Severo Ochoa (CBMSO), Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-8033","authenticated-orcid":false,"given":"Maria Teresa","family":"Valenti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ruggiero","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3822-7166","authenticated-orcid":false,"given":"Elisabetta","family":"Trabetti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-5938","authenticated-orcid":false,"given":"Cristina","family":"Bombieri","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7360-1195","authenticated-orcid":false,"given":"Maria Grazia","family":"Romanelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ruiz-Gabarre, D., Carnero-Espejo, A., \u00c1vila, J., and Garc\u00eda-Escudero, V. (2022). What\u2019s in a Gene? The Outstanding Diversity of MAPT. Cells, 11.","DOI":"10.3390\/cells11050840"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/s41580-024-00753-9","article-title":"Cellular and Pathological Functions of Tau","volume":"25","author":"Naguib","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.bbadis.2004.08.010","article-title":"Tau Gene Alternative Splicing: Expression Patterns, Regulation and Modulation of Function in Normal Brain and Neurodegenerative Diseases","volume":"1739","author":"Andreadis","year":"2005","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Corsi, A., Bombieri, C., Valenti, M.T., and Romanelli, M.G. (2022). Tau Isoforms: Gaining Insight into MAPT Alternative Splicing. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315383"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hong, X., Huang, L., Lei, F., Li, T., Luo, Y., Zeng, M., and Wang, Z. (2025). The Role and Pathogenesis of Tau Protein in Alzheimer\u2019s Disease. Biomolecules, 15.","DOI":"10.3390\/biom15060824"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.brainresbull.2016.08.018","article-title":"Tau and Tauopathies","volume":"126","author":"Arendt","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev-pathmechdis-012418-012936","article-title":"Molecular Pathogenesis of the Tauopathies","volume":"14","author":"Halliday","year":"2019","journal-title":"Annu. Rev. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.tips.2017.03.011","article-title":"A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies","volume":"38","author":"Orr","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12290","DOI":"10.1021\/bi901304u","article-title":"Tau 6D and 6P Isoforms Inhibit Polymerization of Full-Length Tau in Vitro","volume":"48","author":"LaPointe","year":"2009","journal-title":"Biochemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.bbadis.2005.12.003","article-title":"Brain-Specific Change in Alternative Splicing of Tau Exon 6 in Myotonic Dystrophy Type 1","volume":"1762","author":"Leroy","year":"2006","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Basis Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3606","DOI":"10.1002\/alz.13784","article-title":"The Six Brain-Specific TAU Isoforms and Their Role in Alzheimer\u2019s Disease and Related Neurodegenerative Dementia Syndromes","volume":"20","author":"Buchholz","year":"2024","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biochem.72.121801.161720","article-title":"Mechanisms of Alternative Pre-Messenger RNA Splicing","volume":"72","author":"Black","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Juan, W.C., Roca, X., and Ong, S.T. (2014). Identification of Cis-Acting Elements and Splicing Factors Involved in the Regulation of BIM Pre-mRNA Splicing. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095210"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fochi, S., Lorenzi, P., Galasso, M., Stefani, C., Trabetti, E., Zipeto, D., and Romanelli, M.G. (2020). The Emerging Role of the RBM20 and PTBP1 Ribonucleoproteins in Heart Development and Cardiovascular Diseases. Genes, 11.","DOI":"10.3390\/genes11040402"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1261\/rna.2250405","article-title":"Exon Repression by Polypyrimidine Tract Binding Protein","volume":"11","author":"Boutz","year":"2005","journal-title":"RNA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1038\/cdd.2009.87","article-title":"Polypyrimidine Tract Binding Proteins (PTB) Regulate the Expression of Apoptotic Genes and Susceptibility to Caspase-Dependent Apoptosis in Differentiating Cardiomyocytes","volume":"16","author":"Zhang","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.cell.2016.07.025","article-title":"Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex","volume":"166","author":"Zhang","year":"2016","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41590-017-0035-5","article-title":"The RNA-Binding Protein PTBP1 Is Necessary for B Cell Selection in Germinal Centers","volume":"19","author":"Screen","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Suckale, J., Wendling, O., Masjkur, J., J\u00e4ger, M., M\u00fcnster, C., Anastassiadis, K., Stewart, A.F., and Solimena, M. (2011). PTBP1 Is Required for Embryonic Development before Gastrulation. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016992"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"119506","DOI":"10.1016\/j.bbamcr.2023.119506","article-title":"The Role of RNA Splicing Factor PTBP1 in Neuronal Development","volume":"1870","author":"Liu","year":"2023","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/s41593-021-00864-y","article-title":"Therapeutically Viable Generation of Neurons with Antisense Oligonucleotide Suppression of PTB","volume":"24","author":"Maimon","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1016\/j.febslet.2013.07.018","article-title":"Identification of Nuclear Retention Domains in the RBM20 Protein","volume":"587","author":"Filippello","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1038\/nm.2693","article-title":"RBM20, a Gene for Hereditary Cardiomyopathy, Regulates Titin Splicing","volume":"18","author":"Guo","year":"2012","journal-title":"Nat. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.jacc.2009.05.038","article-title":"Mutations in Ribonucleic Acid Binding Protein Gene Cause Familial Dilated Cardiomyopathy","volume":"54","author":"Brauch","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/s41591-020-1087-x","article-title":"Dysregulated Ribonucleoprotein Granules Promote Cardiomyopathy in RBM20 Gene-Edited Pigs","volume":"26","author":"Schneider","year":"2020","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1038\/s41467-019-09483-5","article-title":"Dynamics of Genome Reorganization during Human Cardiogenesis Reveal an RBM20-Dependent Splicing Factory","volume":"10","author":"Bertero","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.biocel.2018.11.009","article-title":"RNA-Binding Proteins RBM20 and PTBP1 Regulate the Alternative Splicing of FHOD3","volume":"106","author":"Lorenzi","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1093\/nar\/gky165","article-title":"Molecular Basis of Titin Exon Exclusion by RBM20 and the Novel Titin Splice Regulator PTB4","volume":"46","author":"Dauksaite","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"RP104808","DOI":"10.7554\/eLife.104808","article-title":"Dilated Cardiomyopathy-Associated RNA-Binding Motif Protein 20 Regulates Long Pre-mRNAs in Neurons","volume":"14","author":"Ortiz","year":"2026","journal-title":"eLife"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2144\/000112208","article-title":"Minigene Reporter for Identification and Analysis of Cis Elements and Trans Factors Affecting Pre-mRNA Splicing","volume":"41","author":"Singh","year":"2006","journal-title":"BioTechniques"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chapelet, G., B\u00e9guin, N., Castellano, B., Grit, I., de Coppet, P., Oullier, T., Neunlist, M., Blotti\u00e8re, H., Rolli-Derkinderen, M., and Le Dr\u00e9an, G. (2023). Tau Expression and Phosphorylation in Enteroendocrine Cells. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1166848"},{"key":"ref_32","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_33","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_34","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/s41596-020-00433-w","article-title":"Generation and Long-Term Culture of Advanced Cerebral Organoids for Studying Later Stages of Neural Development","volume":"16","author":"Giandomenico","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22906","DOI":"10.3390\/ijms141122906","article-title":"New Insights into Functional Roles of the Polypyrimidine Tract-Binding Protein","volume":"14","author":"Romanelli","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1093\/nar\/gkad042","article-title":"PTBP1 Controls Intestinal Epithelial Regeneration through Post-Transcriptional Regulation of Gene Expression","volume":"51","author":"Chembazhi","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/s41416-022-02118-5","article-title":"PTBP1 Drives C-Myc-Dependent Gastric Cancer Progression and Stemness","volume":"128","author":"Ni","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101563","DOI":"10.1016\/j.scr.2019.101563","article-title":"Differentiation of Neural Rosettes from Human Pluripotent Stem Cells in Vitro Is Sequentially Regulated on a Molecular Level and Accomplished by the Mechanism Reminiscent of Secondary Neurulation","volume":"40","author":"Fedorova","year":"2019","journal-title":"Stem Cell Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s12015-006-0011-1","article-title":"Development and Differentiation of Neural Rosettes Derived from Human Embryonic Stem Cells","volume":"2","author":"Wilson","year":"2006","journal-title":"Stem Cell Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13024-022-00533-z","article-title":"Tauopathies: New Perspectives and Challenges","volume":"17","author":"Zhang","year":"2022","journal-title":"Mol. Neurodegener."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"102536","DOI":"10.1016\/j.npep.2025.102536","article-title":"Tauopathies: Emerging Discoveries on Tau Protein, with a Special Focus on Alzheimer\u2019s Disease","volume":"112","author":"Hattiholi","year":"2025","journal-title":"Neuropeptides"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/cm.21812","article-title":"Tau and Neurodegeneration","volume":"81","author":"Goedert","year":"2024","journal-title":"Cytoskeleton"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/biof.1930","article-title":"Tau, Tau Kinases, and Tauopathies: An Updated Overview","volume":"49","author":"Montalto","year":"2023","journal-title":"Biofactors"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1038\/s41380-023-02113-z","article-title":"Does Modulation of Tau Hyperphosphorylation Represent a Reasonable Therapeutic Strategy for Alzheimer\u2019s Disease? From Preclinical Studies to the Clinical Trials","volume":"28","author":"Basheer","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1523\/JNEUROSCI.11-08-02453.1991","article-title":"Tau Gene Expression in Rat Sensory Neurons during Development and Regeneration","volume":"11","author":"Oblinger","year":"1991","journal-title":"J. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41392-024-01734-2","article-title":"Alternative Splicing and Related RNA Binding Proteins in Human Health and Disease","volume":"9","author":"Tao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0169-328X(00)00137-6","article-title":"The Splicing Determinants of a Regulated Exon in the Axonal MAP Tau Reside within the Exon and in Its Upstream Intron","volume":"80","author":"Wei","year":"2000","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1046\/j.1471-4159.2003.02232.x","article-title":"Tau Exon 10, Whose Missplicing Causes Frontotemporal Dementia, Is Regulated by an Intricate Interplay of Cis Elements and Trans Factors","volume":"88","author":"Wang","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1471-4159.2006.04252.x","article-title":"Tau Exon 6 Is Regulated by an Intricate Interplay of Trans Factors and Cis Elements, Including Multiple Branch Points","volume":"100","author":"Wang","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/31508","article-title":"Association of Missense and 5\u2032-Splice-Site Mutations in Tau with the Inherited Dementia FTDP-17","volume":"393","author":"Hutton","year":"1998","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1128\/MCB.01149-10","article-title":"RNA Helicase P68 (DDX5) Regulates Tau Exon 10 Splicing by Modulating a Stem-Loop Structure at the 5\u2032 Splice Site","volume":"31","author":"Kar","year":"2011","journal-title":"Mol. Cell. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1471-4159.2004.02477.x","article-title":"A Minimal Length between Tau Exon 10 and 11 Is Required for Correct Splicing of Exon 10","volume":"90","author":"Yu","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.neuron.2020.06.010","article-title":"Selective Neuronal Vulnerability in Alzheimer\u2019s Disease: A Network-Based Analysis","volume":"107","author":"Roussarie","year":"2020","journal-title":"Neuron"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.32604\/or.2025.060958","article-title":"Splicing Factor PTBP1 Promotes Hepatocarcinogenesis via Oncogenic Splice-Switching of MAPT","volume":"33","author":"Zheng","year":"2025","journal-title":"Oncol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e004355","DOI":"10.1161\/CIRCGEN.123.004355","article-title":"Mechanisms of RBM20 Cardiomyopathy: Insights From Model Systems","volume":"17","author":"Gregorich","year":"2024","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1394","DOI":"10.1002\/wrna.1394","article-title":"Neurodegeneration and RNA-Binding Proteins","volume":"8","author":"Baralle","year":"2017","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102503","DOI":"10.1016\/j.omtn.2025.102503","article-title":"Correcting Tau Isoform Ratios with a Long-Acting Antisense Oligonucleotide Alleviates 4R-Tauopathy Phenotypes","volume":"36","author":"Sahashi","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"ENEURO.0058-20.2020","DOI":"10.1523\/ENEURO.0058-20.2020","article-title":"Increased Tau Expression Correlates with Neuronal Maturation in the Developing Human Cerebral Cortex","volume":"7","author":"Fiock","year":"2020","journal-title":"eNeuro"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12951","DOI":"10.1007\/s12035-025-05100-3","article-title":"Differentiation of SH-SY5Y Cells into Cortical Neuron-like Cells for Tauopathy Modeling and Seeding Assays","volume":"62","author":"Devyatov","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1016\/j.celrep.2016.11.034","article-title":"PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing","volume":"17","author":"Vuong","year":"2016","journal-title":"Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/nn.3026","article-title":"PSD-95 Is Post-Transcriptionally Repressed during Early Neural Development by PTBP1 and PTBP2","volume":"15","author":"Zheng","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.canlet.2015.11.045","article-title":"MYCN Controls an Alternative RNA Splicing Program in High-Risk Metastatic Neuroblastoma","volume":"371","author":"Zhang","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e70675","DOI":"10.1111\/jcmm.70675","article-title":"PTBP1 and Cancer: From RNA Regulation to Therapeutic Potential","volume":"29","author":"Ji","year":"2025","journal-title":"J. Cell. Mol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Koelemen, J., Gotthardt, M., Steinmetz, L.M., and Meder, B. (2021). RBM20-Related Cardiomyopathy: Current Understanding and Future Options. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184101"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1046\/j.1471-4159.1998.70041346.x","article-title":"Splicing of a Regulated Exon Reveals Additional Complexity in the Axonal Microtubule-Associated Protein Tau","volume":"70","author":"Wei","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lid\u00f3n, L., Lla\u00f3-Hierro, L., Nuvolone, M., Aguzzi, A., \u00c1vila, J., Ferrer, I., del R\u00edo, J.A., and Gav\u00edn, R. (2021). Tau Exon 10 Inclusion by PrPC through Downregulating GSK3\u03b2 Activity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105370"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.conb.2021.03.003","article-title":"A Current View on Tau Protein Phosphorylation in Alzheimer\u2019s Disease","volume":"69","author":"Wegmann","year":"2021","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Fernandes, S., Revanna, J., Pratt, J., Hayes, N., Marchetto, M.C., and Gage, F.H. (2024). Modeling Alzheimer\u2019s Disease Using Human Cell Derived Brain Organoids and 3D Models. Front. Neurosci., 18.","DOI":"10.3389\/fnins.2024.1434945"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4547","DOI":"10.1016\/j.cell.2021.07.003","article-title":"ELAVL4, Splicing, and Glutamatergic Dysfunction Precede Neuron Loss in MAPT Mutation Cerebral Organoids","volume":"184","author":"Bowles","year":"2021","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/brain\/awae365","article-title":"Lewy Pathology Formation in Patient-Derived GBA1 Parkinson\u2019s Disease Midbrain Organoids","volume":"148","author":"Frattini","year":"2024","journal-title":"Brain"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Minoia, A., Piritore, F.C., Bolognin, S., Pessoa, J., Bernardes De Jesus, B., Tiso, N., Romanelli, M.G., Schwamborn, J.C., Dalle Carbonare, L., and Valenti, M.T. (2025). Antioxidant, Osteogenic, and Neuroprotective Effects of Homotaurine in Aging and Parkinson\u2019s Disease Models. Antioxidants, 14.","DOI":"10.3390\/antiox14030249"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"3770","DOI":"10.1038\/s41467-023-39420-6","article-title":"Schizophrenia-Associated NRXN1 Deletions Induce Developmental-Timing- and Cell-Type-Specific Vulnerabilities in Human Brain Organoids","volume":"14","author":"Sebastian","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41586-024-07310-6","article-title":"Antisense Oligonucleotide Therapeutic Approach for Timothy Syndrome","volume":"628","author":"Chen","year":"2024","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e70419","DOI":"10.1002\/alz.70419","article-title":"Bezafibrate Treatment Rescues Neurodevelopmental and Neurodegenerative Defects in 3D Cortical Organoid Model of MAPT Frontotemporal Dementia","volume":"21","author":"Cordella","year":"2025","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e70006","DOI":"10.1111\/bpa.70006","article-title":"Herpes Simplex Virus-1 Infection Alters Microtubule-Associated Protein Tau Splicing and Promotes Tau Pathology in Neural Models of Alzheimer\u2019s Disease","volume":"35","author":"Ijezie","year":"2025","journal-title":"Brain Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: Scanning for Occurrences of a given Motif","volume":"27","author":"Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"baw035","DOI":"10.1093\/database\/baw035","article-title":"ATtRACT-a Database of RNA-Binding Proteins and Associated Motifs","volume":"2016","author":"Giudice","year":"2016","journal-title":"Database"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1172\/JCI74523","article-title":"RNA-Binding Protein RBM20 Represses Splicing to Orchestrate Cardiac Pre-mRNA Processing","volume":"124","author":"Maatz","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1038\/s41467-021-22917-3","article-title":"The RNA Binding Protein FgRbp1 Regulates Specific Pre-mRNA Splicing via Interacting with U2AF23 in Fusarium","volume":"12","author":"Wang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1046\/j.1471-4159.2000.0750991.x","article-title":"Sequential Treatment of SH-SY5Y Cells with Retinoic Acid and Brain-Derived Neurotrophic Factor Gives Rise to Fully Differentiated, Neurotrophic Factor-Dependent, Human Neuron-like Cells","volume":"75","author":"Encinas","year":"2000","journal-title":"J. Neurochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4001\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T04:13:12Z","timestamp":1778386392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":81,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27094001"],"URL":"https:\/\/doi.org\/10.3390\/ijms27094001","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]}}}