{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:58:45Z","timestamp":1790395125506,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008608","name":"Sumitomo Foundation","doi-asserted-by":"publisher","award":["200490"],"award-info":[{"award-number":["200490"]}],"id":[{"id":"10.13039\/100008608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In the central nervous system, myelin formed around nerve axons by oligodendrocyte enables efficient conduction of action potentials and maintains axonal homeostasis. Therefore, in demyelinating diseases, such as multiple sclerosis (MS), axonal degeneration and loss, particularly in small\u2010diameter axons, are observed. Teneurin\u20104 deficient (Ten\u20104 \u2010\/\u2010) mice exhibit severe dysmyelination of small\u2010diameter axons, but survive for over a year. Here, we aimed to elucidate the mechanism of the survival of small\u2010diameter axons without myelin using Ten\u20104 \u2010\/\u2010 mice. An immunohistochemical analysis showed abnormally diffused and intense staining of neurofilament. Further, the immunohistochemical signal of nonphosphorylated neurofilament and amyloid precursor protein was higher in Ten\u20104 \u2010\/\u2010 mice. An electron microscopy analysis unexpectedly revealed that small\u2010diameter axons in Ten\u20104 \u2010\/\u2010 mice survived at the age of 1\u2009year, despite the absence of compact myelin. To elucidate the molecular mechanism, we performed a proteomics analysis in the Ten\u20104 \u2010\/\u2010 tissue by mass spectrometry. The result indicated that four of the seven 14\u20103\u20103 isoforms were highly expressed in Ten\u20104 \u2010\/\u2010 small\u2010diameter axons. Finally, when the function of 14\u20103\u20103s in Ten\u20104 \u2010\/\u2010 mice was inhibited by 14\u20103\u20103 inhibitors, BV02 and difopein, the progression of small\u2010diameter axon damage was observed. Altogether, 14\u20103\u20103s are among the pro\u2010survival factors in dysmyelinated small\u2010diameter axons. Our findings may be useful for better understanding the pathogenesis of demyelinating diseases, such as MS, as well as for the development of new treatments.<\/jats:p>","DOI":"10.1002\/glia.70221","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:46:26Z","timestamp":1788957986000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Maintenance of Dysmyelinated Small\u2010Diameter Axons by 14\u20103\u20103s in the Central Nervous System"],"prefix":"10.1002","volume":"74","author":[{"given":"Nanako","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Clinical Bioanalysis and Molecular Biology, Graduate School of Medical and Dental Sciences Institute of Science Tokyo\/Tokyo Medical and Dental University (TMDU)  Tokyo 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