{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:06:36Z","timestamp":1788581196457,"version":"build-2803163510"},"reference-count":133,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tau protein is a microtubule-associated protein encoded by the MAPT gene that carries out a myriad of physiological functions and has been linked to certain pathologies collectively termed tauopathies, including Alzheimer\u2019s disease, frontotemporal dementia, Huntington\u2019s disease, progressive supranuclear palsy, etc. Alternative splicing is a physiological process by which cells generate several transcripts from one single gene and may in turn give rise to different proteins from the same gene. MAPT transcripts have been proven to be subjected to alternative splicing, generating six main isoforms in the central nervous system. Research throughout the years has demonstrated that the splicing landscape of the MAPT gene is far more complex than that, including at least exon skipping events, the use of 3\u2032 and 5\u2032 alternative splice sites and, as has been recently discovered, also intron retention. In addition, MAPT alternative splicing has been showed to be regulated spatially and developmentally, further evidencing the complexity of the gene\u2019s splicing regulation. It is unclear what would drive the need for the existence of so many isoforms encoded by the same gene, but a wide range of functions have been ascribed to these Tau isoforms, both in physiology and pathology. In this review we offer a comprehensive up-to-date exploration of the mechanisms leading to the outstanding diversity of isoforms expressed from the MAPT gene and the functions in which such isoforms are involved, including their potential role in the onset and development of tauopathies such as Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3390\/cells11050840","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T08:17:03Z","timestamp":1646122623000},"page":"840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["What\u2019s in a Gene? The Outstanding Diversity of MAPT"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-1191","authenticated-orcid":false,"given":"Daniel","family":"Ruiz-Gabarre","sequence":"first","affiliation":[{"name":"Anatomy, Histology and Neuroscience Department, School of Medicine, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (UAM-CSIC), 28049 Madrid, Spain"},{"name":"Graduate Program in Neuroscience, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-0289","authenticated-orcid":false,"given":"Almudena","family":"Carnero-Espejo","sequence":"additional","affiliation":[{"name":"Anatomy, Histology and Neuroscience Department, School of Medicine, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"},{"name":"Graduate Program in Neuroscience, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6288-0571","authenticated-orcid":false,"given":"Jes\u00fas","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (UAM-CSIC), 28049 Madrid, Spain"},{"name":"Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, 28031 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-0882","authenticated-orcid":false,"given":"Vega","family":"Garc\u00eda-Escudero","sequence":"additional","affiliation":[{"name":"Anatomy, Histology and Neuroscience Department, School of Medicine, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"},{"name":"Centro de Biolog\u00eda Molecular Severo Ochoa (UAM-CSIC), 28049 Madrid, Spain"},{"name":"Graduate Program in Neuroscience, Universidad Aut\u00f3noma de Madrid (UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","article-title":"Tau protein isoforms, phosphorylation and role in neurodegenerative disorders","volume":"33","author":"Delacourte","year":"2000","journal-title":"Brain Res. 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