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http://purl.uniprot.org/citations/34060470http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34060470http://www.w3.org/2000/01/rdf-schema#comment"Traumatic brain injury (TBI) is a predisposing factor for many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and chronic traumatic encephalopathy (CTE). Although defects in nucleocytoplasmic transport (NCT) is reported ALS and other neurodegenerative diseases, whether defects in NCT occur in TBI remains unknown. We performed proteomic analysis on Drosophila exposed to repeated TBI and identified resultant alterations in several novel molecular pathways. TBI upregulated nuclear pore complex (NPC) and nucleocytoplasmic transport (NCT) proteins as well as alter nucleoporin stability. Traumatic injury disrupted RanGAP1 and NPC protein distribution in flies and a rat model and led to coaggregation of NPC components and TDP-43. In addition, trauma-mediated NCT defects and lethality are rescued by nuclear export inhibitors. Importantly, genetic upregulation of nucleoporins in vivo and in vitro triggered TDP-43 cytoplasmic mislocalization, aggregation, and altered solubility and reduced motor function and lifespan of animals. We also found NUP62 pathology and elevated NUP62 concentrations in postmortem brain tissues of patients with mild or severe CTE as well as co-localization of NUP62 and TDP-43 in CTE. These findings indicate that TBI leads to NCT defects, which potentially mediate the TDP-43 pathology in CTE."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.org/dc/terms/identifier"doi:10.7554/elife.67587"xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Schwartz J.C."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Cherry J.D."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Kofler J."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Ramesh N."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Donnelly C.J."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Anderson E.N."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Kour S."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Pandey U.B."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Old W."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Stein T.D."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Cheng J.P."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Kline A.E."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Morera A.A."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Ebmeier C."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/author"Gleixner A."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/name"Elife"xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/pages"e67587"xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/title"Traumatic injury compromises nucleocytoplasmic transport and leads to TDP-43 pathology."xsd:string
http://purl.uniprot.org/citations/34060470http://purl.uniprot.org/core/volume"10"xsd:string
http://purl.uniprot.org/citations/34060470http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34060470
http://purl.uniprot.org/citations/34060470http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34060470