{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:09:28Z","timestamp":1779296968813,"version":"3.51.4"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS434"],"award-info":[{"award-number":["ZR2025MS434"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Neurofilaments (NFs) are the predominant type IV intermediate filaments in differentiated neurons, functioning not just as static scaffolds, but as active drivers of radial axonal growth and nerve conduction velocity. While their physical properties are well characterized, a critical gap remains in synthesizing how their dynamic assembly and developmental subunit switching directly dictate neurodegenerative outcomes. This review breaks down the molecular architecture and stepwise kinetic assembly of NFs, detailing their role in polarized transport and the formation of a protective viscoelastic gel network within axons. We specifically highlight the physiological expression switching of early subunits, such as alpha-internexin and peripherin, during neuronal maturation, a process often overlooked in traditional structural reviews. By examining how specific gene mutations and aberrant hyperphosphorylation trigger axonal transport jams and protein aggregation, we map the direct pathways leading to amyotrophic lateral sclerosis (ALS) and Charcot\u2013Marie\u2013Tooth (CMT) disease. Finally, we emphasize that a precise mechanistic decoding of NF structural dynamics and their pathological disruption is essential for understanding the fundamental etiology of these neurodegenerative conditions.<\/jats:p>","DOI":"10.3390\/neurosci7030058","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:45:34Z","timestamp":1779291934000},"page":"58","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Axonal Growth to Neurodegeneration: The Dual Role of Neurofilament Dynamics in Health and Disease"],"prefix":"10.3390","volume":"7","author":[{"given":"Yikang","family":"An","sequence":"first","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongying","family":"Lan","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialong","family":"Xiong","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoyan","family":"Jing","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongjin","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinping","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5969-6407","authenticated-orcid":false,"given":"Qi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Cancer Centre, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"},{"name":"MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR 999078, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9403-4337","authenticated-orcid":false,"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science, Beijing Institute of Technology, Beijing 100081, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1523\/JNEUROSCI.08-04-01454.1988","article-title":"The establishment of polarity by hippocampal neurons in culture","volume":"8","author":"Dotti","year":"1988","journal-title":"J. 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