{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T01:11:29Z","timestamp":1789780289699,"version":"4.0.1"},"reference-count":70,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K22NS125057"],"award-info":[{"award-number":["K22NS125057"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Charcot\u2013Marie\u2013Tooth Disease Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) are the most common inherited peripheral neuropathies and arise from copy number variation of the Peripheral Myelin Protein 22 (\n                    <jats:italic>PMP22<\/jats:italic>\n                    ) gene. While secondary axon degeneration has been proposed as the primary driver of disability, our prior work demonstrated pronounced neuromuscular impairment in CMT1A model mice in the absence of overt axonal loss, prompting investigation into primary myelin dysfunction. Here, we reveal that altered\n                    <jats:italic>PMP22<\/jats:italic>\n                    dosage profoundly disrupts molecular architecture at critical myelin domains, Schmidt\u2010Lanterman incisures (SLIs) and Nodes of Ranvier. Using high\u2010resolution confocal imaging of teased peripheral nerve fibers from CMT1A and HNPP model mice, we identified widespread disorganization of adherens junctions, mislocalization of Connexin29 and aberrant distribution of nodal ion channels, with several defects more severe in CMT1A, consistent with disease burden. Notably, nodal widening and abnormal spreading of Kv1.2 and Caspr along internodes indicate compromised axo\u2010glial compartmentalization essential for saltatory conduction. Together, these findings support a model in which\n                    <jats:italic>PMP22<\/jats:italic>\n                    functions as a structural organizer of myelin, coordinating adherens junction patterning and nodal subdomain integrity. Dysregulation of this function is predicted to compromise Schwann\u2010cell architecture, metabolic support and axonal excitability. Our findings support a paradigm shift in which molecular destabilization of myelin, rather than secondary axonal degeneration alone, contributes to disease progression in CMT1A and HNPP. This work also identifies junctional complexes as potential actionable molecular targets and establishes a mechanistic framework applicable to a broad spectrum of inherited dysmyelinating and acquired demyelinating neuropathies.\n                  <\/jats:p>","DOI":"10.1002\/glia.70124","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T11:27:27Z","timestamp":1765884447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Aberrant Molecular Myelin Architecture in Charcot\u2013Marie\u2013Tooth Disease Type\n                    <scp>1A<\/scp>\n                    and Hereditary Neuropathy With Liability to Pressure Palsies"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3726-4056","authenticated-orcid":false,"given":"Kathryn R.","family":"Moss","sequence":"first","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation University of Missouri School of Medicine  Columbia Missouri USA"},{"name":"NextGen Precision Health University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvis A.","family":"Arowolo","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation University of Missouri School of Medicine  Columbia Missouri USA"},{"name":"NextGen Precision Health University of Missouri  Columbia Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave R.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuromuscular Division Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1215-3373","authenticated-orcid":false,"given":"Ahmet","family":"H\u00f6ke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuromuscular Division Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-12-04662.1997"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1195-274"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06458.2002"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-12-04545.1997"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1007009613484"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09319-8"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02838-y"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.4.1095"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12990-015-0065-7"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-025-03479-w"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8266101"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10089"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623319850773"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090034797"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00688-7"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.16457"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20315"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.4.846"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183211"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.129.1.189"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(99)00049-0"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24086"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15231"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu257"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01190831"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006290"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1486576"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394311-8.00018-2"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.7.1516"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44321-023-00019-5"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/019262330002800114"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8370-x"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13079"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2000508117"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.62.4.310"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23578"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi500809t"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90472-3"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/jns.12483"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9565"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19991201)58:5<612::AID-JNR2>3.0.CO;2-X"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.251548398"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1159\/000505815"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.110989"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041361"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01077.2015"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00039.x"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-07-0551"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20154"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8027.2002.02001.x"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199809)24:1<8::AID-GLIA2>3.0.CO;2-3"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21992"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.4161\/tisb.25502"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-53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