{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:50:00Z","timestamp":1785408600995,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Research, Technology and Space of Germany","doi-asserted-by":"publisher","award":["01EK1606A"],"award-info":[{"award-number":["01EK1606A"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"award":["01EK1606A"],"award-info":[{"award-number":["01EK1606A"]}],"id":[{"id":"https:\/\/ror.org\/04pz7b180","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002957","name":"Technische Universit\u00e4t Dresden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002957","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/042aqky30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tau protein aggregation and spreading are central features of neurodegenerative diseases such as Alzheimer\u2019s disease and frontotemporal dementia. Here, we investigated the role of phosphatidylinositol 4-kinase type III\u03b1 (PI4KIII\u03b1) in regulating tau propagation. We first used tau biosensor cells to demonstrate that both pharmacological inhibition and genetic reduction in PI4KIII\u03b1 effectively reduce the seeding of tau aggregation by extracellular seeds. To extend these findings to a more physiologically relevant system, we generated induced pluripotent stem (iPS) cell-derived cortical neurons carrying pathogenic MAPT mutations. These neurons rapidly acquired tauopathy-associated features, including expression of disease-relevant isoforms such as 4R tau, thereby enabling in vitro modeling of tau pathology. Using this model, we established phenotypic assays to monitor tau propagation and aggregation and applied them to test candidate small molecules. Notably, inhibition of PI4KIII\u03b1 consistently reduced seeding of tau assemblies in human neurons, highlighting this kinase as an important player in the seeding of tau pathology. Collectively, our work identifies PI4KIII\u03b1 as a regulator of tau pathology and provides new experimental platforms to dissect the molecular mechanisms of tau propagation. These findings open potential avenues for the development of strategies to slow or prevent tau-mediated neurodegeneration in the central nervous system.<\/jats:p>","DOI":"10.3390\/cells15131228","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:04:49Z","timestamp":1783411489000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reducing PI4KIII\u03b1 Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8490-5458","authenticated-orcid":false,"given":"Eleonora","family":"Clemente","sequence":"first","affiliation":[{"name":"Center for Regenerative Therapies TU Dresden (CRTD), Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishnan","family":"Sivasubramanian","sequence":"additional","affiliation":[{"name":"Center for Regenerative Therapies TU Dresden (CRTD), Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0326-8809","authenticated-orcid":false,"given":"Susanne","family":"Kordes","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, 44227 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Center for Regenerative Therapies TU Dresden (CRTD), Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Max Delbr\u00fcck Center, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9125-3705","authenticated-orcid":false,"given":"Ruth","family":"Hans","sequence":"additional","affiliation":[{"name":"Light Microscopy Facility, Center for Molecular and Cellular Bioengineering (CMCB), Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Vogel","sequence":"additional","affiliation":[{"name":"Center for Regenerative Therapies TU Dresden (CRTD), Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Physics of Life, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Baumann","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, 44227 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5475-9053","authenticated-orcid":false,"given":"Bert","family":"Klebl","sequence":"additional","affiliation":[{"name":"Lead Discovery Center GmbH, 44227 Dortmund, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7688-3124","authenticated-orcid":false,"given":"Jared","family":"Sterneckert","sequence":"additional","affiliation":[{"name":"Center for Regenerative Therapies TU Dresden (CRTD), Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"},{"name":"Medical Faculty Carl Gustav Carus of TU Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tabeshmehr, P., and Eftekharpour, E. 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