{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:17:46Z","timestamp":1791231466519,"version":"4.1.0"},"reference-count":105,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG079898"],"award-info":[{"award-number":["R01AG079898"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007259","name":"Stony Brook University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007259","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neurodegenerative diseases (NDDs) and other age\u2010related disorders have been classically defined by a set of key pathological hallmarks. Two of these hallmarks, cell cycle dysregulation (CCD) and nucleocytoplasmic transport (NCT) defects, have long been debated as being either causal or consequential in the pathology of accelerated aging. Specifically, aberrant cell cycle activation in post\u2010mitotic neurons has been shown to trigger neuronal cell death pathways and cellular senescence. Additionally, NCT has been observed to be progressively dysregulated during aging and in neurodegeneration, where the increased subcellular redistribution of nuclear proteins, such as TAR DNA\u2010Binding Protein\u201043 (TDP\u201043), to the cytoplasm is a primary driver of disease. However, the functional significance of NCT defects as either a causal mechanism or consequence of pathology, and how the redistribution of cell cycle machinery contributes to neurodegeneration, remains unclear. Here, we describe that pharmacological inhibition of importin\u2010\u03b2 nuclear import is capable of perturbing cell cycle machinery both in mitotic neuronal cell lines and post\u2010mitotic primary neurons in\u00a0vitro. Our\n                    <jats:italic>Nemf<\/jats:italic>\n                    <jats:sup>R86S<\/jats:sup>\n                    mouse model of motor neuron disease, characterized by nuclear import defects, further recapitulates the hallmarks of CCD we observed in mitotic cell lines and in post\u2010mitotic primary neurons in\u00a0vitro, and in spinal motor neurons in\u00a0vivo. The observed CCD is consistent with the transcriptional and phenotypical dysregulation commonly associated with neuronal cell death and senescence\u2010like features in NDDs. Together, this evidence suggests that impairment of nuclear import pathways resulting in CCD may be a common driver of pathology in neurodegeneration.\n                  <\/jats:p>","DOI":"10.1111\/acel.70091","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:16:38Z","timestamp":1747376198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nuclear Import Defects Drive Cell Cycle Dysregulation in Neurodegeneration"],"prefix":"10.1111","volume":"24","author":[{"given":"Jonathan","family":"Plessis\u2010Belair","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Behavior Stony Brook University  Stony Brook New York USA"},{"name":"Center for Nervous System Disorders Stony Brook University  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior Stony Brook University  Stony Brook New York USA"},{"name":"Center for Nervous System Disorders Stony Brook University  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2592-5045","authenticated-orcid":false,"given":"Markus","family":"Riessland","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior Stony Brook University  Stony Brook New York USA"},{"name":"Center for Nervous System Disorders Stony Brook University  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3327-537X","authenticated-orcid":false,"given":"Roger B.","family":"Sher","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior Stony Brook University  Stony Brook New York USA"},{"name":"Center for Nervous System Disorders Stony Brook University  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23765"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2004.11.025"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp9556"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq5622"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-016-0111-6"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.1.2.108"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/332546a0"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061138"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2825349"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535\u20106108(03)00080\u20101"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2018.1534524"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204385"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3219"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9872"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59419"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.11.037"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e26393"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.039"},{"key":"e_1_2_10_20_1","first-page":"235","article-title":"Cyclin\u2010Dependent Kinase Inhibitors","volume":"5","author":"Fischer P. 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