{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:25:41Z","timestamp":1789896341320,"version":"4.0.1"},"reference-count":48,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":1282,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN184584"],"award-info":[{"award-number":["FRN184584"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007476","name":"Canadian Diabetes Association","doi-asserted-by":"publisher","award":["OG-3-12-3669"],"award-info":[{"award-number":["OG-3-12-3669"]}],"id":[{"id":"10.13039\/100007476","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008459","name":"University of Calgary","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003179","name":"Alberta Heritage Foundation for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003179","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Hospital Foundation, Edmonton"},{"DOI":"10.13039\/501100000190","name":"University of Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Unique deficits in the function of adult sensory neurons as part of their early neurodegeneration might account for progressive polyneuropathy during chronic diabetes mellitus. Here, we provide structural and functional evidence for aberrant pre-mRNA splicing in a chronic type 1 model of experimental diabetic polyneuropathy (DPN). Cajal bodies (CBs), unique nuclear substructures involved in RNA splicing, increased in number in diabetic sensory neurons, but their expected colocalization with survival motor neuron (SMN) proteins was reduced \u2013 a mislocalization described in motor neurons of spinal muscular atrophy. Small nuclear ribonucleoprotein particles (snRNPs), also participants in the spliceosome, had abnormal multiple nuclear foci unassociated with CBs, and their associated snRNAs were reduced. CWC22, a key spliceosome protein, was aberrantly upregulated in diabetic dorsal root ganglia (DRG), and impaired neuronal function. CWC22 attenuated sensory neuron plasticity, with knockdown in vitro enhancing their neurite outgrowth. Further, axonal delivery of CWC22 siRNA unilaterally to locally knock down the aberrant protein in diabetic nerves improved aspects of sensory function in diabetic mice. Collectively, our findings identify subtle but significant alterations in spliceosome structure and function, including dysregulated CBs and CWC22 overexpression, in diabetic sensory neurons that offer new ideas regarding diabetic sensory neurodegeneration in polyneuropathy.<\/jats:p>","DOI":"10.1242\/dmm.028225","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T14:25:14Z","timestamp":1488378314000},"page":"215-224","source":"Crossref","is-referenced-by-count":32,"title":["Diabetic polyneuropathy, sensory neurons, nuclear structure and spliceosome alterations: a role for CWC22"],"prefix":"10.1242","volume":"10","author":[{"given":"Masaki","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Division of Neurology and Department of Medicine, Faculty of Medicine and Dentistry, and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada, T6G 2G3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambika","family":"Chandrasekhar","sequence":"additional","affiliation":[{"name":"Division of Neurology and Department of Medicine, Faculty of Medicine and Dentistry, and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada, T6G 2G3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and\u2008Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Canada, T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and\u2008Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Canada, T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilarie","family":"Ng","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and\u2008Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Canada, T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane","family":"de la Hoz","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain Institute and\u2008Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Canada, T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1692-5983","authenticated-orcid":false,"given":"Douglas W.","family":"Zochodne","sequence":"additional","affiliation":[{"name":"Division of Neurology and Department of Medicine, Faculty of Medicine and Dentistry, and the Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Canada, T6G 2G3"},{"name":"Hotchkiss Brain Institute and\u2008Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary, Canada, T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042500062930200_DMM028225C1","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1084\/jem.173.6.1407","article-title":"Human autoantibody to a novel protein of the nuclear coiled body: immunological characterization and cDNA cloning of p80-coilin","volume":"173","author":"Andrade","year":"1991","journal-title":"J. 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