{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:08:19Z","timestamp":1791986899172,"version":"4.4.0"},"reference-count":77,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Faculty of the University of Freiburg","award":["2021\/A3-Sch"],"award-info":[{"award-number":["2021\/A3-Sch"]}]},{"name":"Medical Faculty of the University of Freiburg","award":["413517907"],"award-info":[{"award-number":["413517907"]}]},{"name":"Medical Faculty of the University of Freiburg","award":["SCHA 1442\/8-1"],"award-info":[{"award-number":["SCHA 1442\/8-1"]}]},{"name":"Medical Faculty of the University of Freiburg","award":["1442\/9-1"],"award-info":[{"award-number":["1442\/9-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["2021\/A3-Sch"],"award-info":[{"award-number":["2021\/A3-Sch"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["413517907"],"award-info":[{"award-number":["413517907"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["SCHA 1442\/8-1"],"award-info":[{"award-number":["SCHA 1442\/8-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["1442\/9-1"],"award-info":[{"award-number":["1442\/9-1"]}]},{"name":"German Research Foundation Grant (DFG)","award":["2021\/A3-Sch"],"award-info":[{"award-number":["2021\/A3-Sch"]}]},{"name":"German Research Foundation Grant (DFG)","award":["413517907"],"award-info":[{"award-number":["413517907"]}]},{"name":"German Research Foundation Grant (DFG)","award":["SCHA 1442\/8-1"],"award-info":[{"award-number":["SCHA 1442\/8-1"]}]},{"name":"German Research Foundation Grant (DFG)","award":["1442\/9-1"],"award-info":[{"award-number":["1442\/9-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nuclear pore complexes (NPCs) are highly dynamic macromolecular protein structures that facilitate molecular exchange across the nuclear envelope. Aberrant NPC functioning has been implicated in neurodegeneration. The translocated promoter region (Tpr) is a critical scaffolding nucleoporin (Nup) of the nuclear basket, facing the interior of the NPC. However, the role of Tpr in adult neural stem\/precursor cells (NSPCs) in Alzheimer\u2019s disease (AD) is unknown. Using super-resolution (SR) and electron microscopy, we defined the different subcellular localizations of Tpr and phospho-Tpr (P-Tpr) in NSPCs in vitro and in vivo. Elevated Tpr expression and reduced P-Tpr nuclear localization accompany NSPC differentiation along the neurogenic lineage. In 5xFAD mice, an animal model of AD, increased Tpr expression in DCX+ hippocampal neuroblasts precedes increased neurogenesis at an early stage, before the onset of amyloid-\u03b2 plaque formation. Whereas nuclear basket Tpr interacts with chromatin modifiers and NSPC-related transcription factors, P-Tpr interacts and co-localizes with cyclin-dependent kinase 1 (Cdk1) at the nuclear chromatin of NSPCs. In hippocampal NSPCs in a mouse model of AD, aberrant Tpr expression was correlated with altered NPC morphology and counts, and Tpr was aberrantly expressed in postmortem human brain samples from patients with AD. Thus, we propose that altered levels and subcellular localization of Tpr in CNS disease affect Tpr functionality, which in turn regulates the architecture and number of NSPC NPCs, possibly leading to aberrant neurogenesis.<\/jats:p>","DOI":"10.3390\/cells12232757","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T10:39:48Z","timestamp":1701427188000},"page":"2757","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Tpr Misregulation in Hippocampal Neural Stem Cells in Mouse Models of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Subash C.","family":"Malik","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Di","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Ziegler-Waldkirch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4746-2356","authenticated-orcid":false,"given":"Stefan","family":"Tholen","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, Medical Center, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin S.","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2205-5427","authenticated-orcid":false,"given":"Marius","family":"Schwabenland","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Schilling","sequence":"additional","affiliation":[{"name":"Institute of Surgical Pathology, Medical Center, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-3770","authenticated-orcid":false,"given":"Andreas","family":"Vlachos","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Center BrainLinks-BrainTools, University of Freiburg, 79110 Freiburg, Germany"},{"name":"Center for Basics in Neuromodulation (NeuroModul Basics), Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Meyer-Luehmann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"},{"name":"Center for Basics in Neuromodulation (NeuroModul Basics), Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9851-6299","authenticated-orcid":false,"given":"Christian","family":"Schachtrup","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, University of Freiburg, 79104 Freiburg, Germany"},{"name":"Center for Basics in Neuromodulation (NeuroModul Basics), Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1523\/JNEUROSCI.22-03-00629.2002","article-title":"Neurogenesis in adult subventricular zone","volume":"22","year":"2002","journal-title":"J. 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