{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:04Z","timestamp":1786978024630,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T00:00:00Z","timestamp":1691539200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The functional deterioration and loss of motor neurons are tightly associated with degenerative motor neuron diseases and aging\u2010related muscle wasting. Motor neuron diseases or aging\u2010related muscle wasting in turn contribute to increased risk of adverse health outcomes in the elderly. Cdon (cell adhesion molecule\u2010downregulated oncogene) belongs to the immunoglobulin superfamily of cell adhesion molecule and plays essential roles in multiple signalling pathways, including sonic hedgehog (Shh), netrin, and cadherin\u2010mediated signalling. Cdon as a Shh coreceptor plays a critical role in motor neuron specification during embryonic development. However, its role in adult motor neuron function is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Hb9\u2010Cre recombinase\u2010driven motor neuron\u2010specific Cdon deficient mice (mnKO) and a compound mutant mice (mnKO::SOD1\n                      <jats:sup>G93A<\/jats:sup>\n                      ) were generated to investigate the role of Cdon in motor neuron degeneration. Motor neuron regeneration was examined by using a sciatic nerve crush injury model. To investigate the phenotype, physical activity, compound muscle action potential, immunostaining, and transmission electron microscopy were carried out. In the mechanism study, RNA sequencing and RNA\/protein analyses were employed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mice lacking Cdon in motor neurons exhibited middle age onset lethality and aging\u2010related decline in motor function. In the sciatic nerve crush injury model, mnKO mice exhibited an impairment in motor function recovery evident by prolonged compound muscle action potential duration (4.63\u00a0\u00b1\u00a00.35 vs. 3.93\u00a0\u00b1\u00a00.22\u00a0s for f\/f,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.01) and physical activity. Consistently, neuromuscular junctions of mnKO muscles were incompletely occupied (49.79\u00a0\u00b1\u00a05.74 vs. 79.39\u00a0\u00b1\u00a03.77% fully occupied neuromuscular junctions for f\/f,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001), suggesting an impaired reinnervation. The transmission electron microscopy analysis revealed that mnKO sciatic nerves had smaller axon diameter (0.88\u00a0\u00b1\u00a00.13 vs. 1.43\u00a0\u00b1\u00a00.48\u00a0\u03bcm for f\/f,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001) and myelination defects. RNA sequencing of mnKO lumbar spinal cords showed alteration in genes related to neurogenesis, inflammation and cell death. Among the altered genes, ErbB4 and FgfR expressions were significantly altered in mnKO as well as in Cdon\u2010depleted NSC34 motor neuron cells. Consistently, Cdon\u2010depleted NSC34 cells exhibited elevated levels of cleaved Caspase3 and \u03b3H2AX proteins, as well as Bax transcription. Cdon\u2010depleted NSC34 cells also exhibited impaired activation of Akt in response to neuregulin\u20101 (NRG1) treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our current data demonstrate the functional importance of Cdon in motor neuron function and nerve repair. Cdon ablation causes alterations in neurotrophin signalling that leads to motor neuron degeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13308","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T02:00:51Z","timestamp":1691632851000},"page":"2239-2252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cdon ablation in motor neurons causes age\u2010related motor neuron degeneration and impaired sciatic nerve repair"],"prefix":"10.1002","volume":"14","author":[{"given":"Sunghee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subin","family":"An","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Research Institute of Animuscure INC  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yideul","family":"Jeong","sequence":"additional","affiliation":[{"name":"Research Institute of Animuscure INC  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Lim","family":"You","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyebeen","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju\u2010Hyeon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae\u2010Eun","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongryul","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyu\u2010Un","family":"Bae","sequence":"additional","affiliation":[{"name":"College of Pharmacy Sookmyung Women's University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9072-8211","authenticated-orcid":false,"given":"Jong\u2010Sun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology Sungkyunkwan University School of Medicine  Suwon South Korea"},{"name":"Single Cell Network Research Center Sungkyunkwan University School of Medicine  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2007.05.040"},{"key":"e_1_2_7_3_1","first-page":"709","article-title":"Age\u2010related changes in motor function (I). 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