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This pathological process results in muscle weakness and can culminate in paralysis. To date, the precise etiology of ALS remains unclear. However, a burgeoning body of research indicates that axonal dysfunction is a pivotal element in the pathogenesis of ALS and significantly influences the progression of disease. Dysfunction of axons in ALS can result in impediments to nerve impulse transmission, leading to motor impairment, muscle atrophy, and other associated complications that severely compromise patients\u2019 quality of life and survival prognosis. In this review, we concentrate on several key areas: the ultrastructure of axons, the mechanisms of axonal degeneration in ALS, the impact of impaired axonal transport on disease progression in ALS, and the potential for axonal regeneration within the central nervous system (CNS). Our objective is to achieve a more holistic and profound understanding of the multifaceted role that axons play in ALS, thereby offering a more intricate and refined perspective on targeted axonal therapeutic interventions.<\/jats:p>","DOI":"10.3390\/cells13242076","type":"journal-article","created":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T03:46:02Z","timestamp":1734407162000},"page":"2076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Exploring the Role of Axons in ALS from Multiple Perspectives"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiaosu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, China"},{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Shandong Second Medical University, Weifang 261053, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Liu","sequence":"additional","affiliation":[{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiupeng","family":"Yan","sequence":"additional","affiliation":[{"name":"Neurologic Disorders and Regenerative Repair Lab of Shandong Higher Education, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Zhou","sequence":"additional","affiliation":[{"name":"Neurologic Disorders and 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