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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:p>\n                    Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) develop as spatial pathologies in which neurons and glial cells are interconnected. TAR DNA-binding protein 43 (TDP-43) is a major pathological protein that is inextricably associated with ALS and FTLD. In this study, we investigated the roles of neuronal TDP-43 in neuron\u2013oligodendrocyte interactions using neuron-specific TDP-43 knockout (TDP-43cKO) mice. TDP-43 depletion in neurons induced hypomyelination, which was confirmed by immunohistochemistry and ultrastructural analysis. In addition, conduction disturbance was revealed by electrophysiological analysis. The hypomyelination of TDP-43cKO mouse was restored by cytoplasmic TDP-43 supplementation in neurons. Neuron-specific transcriptome analysis revealed that neurexin 1 (NRXN1) is the regulatory target of TDP-43, which promotes myelin formation. The hypomyelination of TDP-43cKO mice was also restored by NRXN1b supplementation in neurons. We further confirmed that TDP-43 stabilizes\n                    <jats:italic toggle=\"yes\">Nrxn1<\/jats:italic>\n                    mRNA by binding to the\n                    <jats:italic toggle=\"yes\">Nrxn1<\/jats:italic>\n                    3\u2019untranslated region (3\u2019UTR). Although TDP-43cKO exhibited impaired recognition memory, the supplementation of NRXN1 in the hippocampus recovered the memory disturbances. In conclusion, this study demonstrates the neuron\u2013oligodendrocyte interaction mediated by neuronal TDP-43 via NRXN1 mRNA stabilization. These findings shed light on neuron\u2013oligodendrocyte interaction in the disease mechanisms of ALS\/FTLD.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2513642123","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T16:52:02Z","timestamp":1772038322000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Neuronal TDP-43 regulates myelin formation via neurexin 1 mRNA stabilization"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3931-0378","authenticated-orcid":false,"given":"Jiayi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Nagoya University Graduate School of Medicine","place":["Nagoya, Aichi, 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Li Neuronal TDP-43 regulates myelin formation via neurexin 1 mRNA stabilization. Gene Expression Omnibus Database. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE246657. 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