{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:22:47Z","timestamp":1792264967934,"version":"4.4.0"},"reference-count":145,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background: Neurodegenerative diseases, including Alzheimer\u2019s disease, Parkinson\u2019s disease, multiple sclerosis, and amyotrophic lateral sclerosis, represent a major global health burden and share convergent pathogenic mechanisms, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, calcium imbalance, and neuronal loss. Despite advances in symptomatic management, effective disease-modifying therapies remain limited. Objectives: This review aims to critically synthesize mechanistic, preclinical, and clinical evidence on \u03b1-lipoic acid and biotin as candidate neuroprotective agents in neurodegenerative diseases, with emphasis on shared signaling pathways, therapeutic potential, generally favorable safety profiles, and translational limitations. Methods: A narrative and integrative review was conducted, encompassing mechanistic studies, preclinical experimental models, and clinical trials and observational studies evaluating ALA and biotin in neurodegenerative diseases. The evidence was qualitatively analyzed with attention to biological plausibility, consistency across models, and clinical relevance. Results: ALA and biotin modulate key cellular pathways implicated in neurodegeneration, including mitochondrial metabolism, redox homeostasis, inflammatory signaling, and neurovascular function. Preclinical studies consistently report beneficial effects on mitochondrial efficiency, oxidative stress, and neuroinflammatory markers. In contrast, clinical evidence remains heterogeneous, with more extensive evaluation of biotin in progressive multiple sclerosis and more limited or exploratory findings for ALA across neurodegenerative disorders. Conclusions: ALA and biotin exhibit mechanistic convergence across pathways relevant to neurodegeneration and generally favorable safety profiles. Although current evidence supports their biological plausibility as adjunctive or exploratory therapeutic strategies, clinical outcomes remain inconsistent and appear to be influenced by dosing regimens, disease stage at intervention, and endpoint selection. Well-designed clinical studies are required to define their efficacy, optimal dosing, and disease-specific applicability.<\/jats:p>","DOI":"10.3390\/neurolint18040064","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:50:15Z","timestamp":1774533015000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Alpha-Lipoic Acid and Biotin in Neurodegenerative Diseases: Convergent Mechanistic Insights from Preclinical Models to Clinical Perspectives"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-2068","authenticated-orcid":false,"given":"Asdrubal","family":"Aguilera-M\u00e9ndez","sequence":"first","affiliation":[{"name":"Institute of Chemical-Biological Research, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Aguilera-Manuel","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biological Sciences, \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58020, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0811-2950","authenticated-orcid":false,"given":"Alfredo","family":"Saavedra-Molina","sequence":"additional","affiliation":[{"name":"Institute of Chemical-Biological Research, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"R\u00edos-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-7393","authenticated-orcid":false,"given":"Santiago","family":"Villafa\u00f1a","sequence":"additional","affiliation":[{"name":"Graduate Studies and Research Section, Higher School of Medicine, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-1942","authenticated-orcid":false,"given":"Renato","family":"Nieto-Aguilar","sequence":"additional","affiliation":[{"name":"Division of Graduate Studies and Research, Faculty of Dentistry, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58337, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-8789","authenticated-orcid":false,"given":"Daniel","family":"God\u00ednez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Institute of Chemical-Biological Research, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58030, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ortega-Cuellar","sequence":"additional","affiliation":[{"name":"Experimental Nutrition Laboratory, National Institute of Pediatrics, Ministry of Health, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2357-814X","authenticated-orcid":false,"given":"Zoraya","family":"Palomera-Sanchez","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine and Animal Science, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-0471","authenticated-orcid":false,"given":"Marcia","family":"Gauthereau-Torres","sequence":"additional","affiliation":[{"name":"Division of Graduate Studies, Faculty of Medicine and Biological Sciences, \u201cDr. Ignacio Ch\u00e1vez\u201d, Universidad Michoacana de San Nicol\u00e1s de Hidalgo, Morelia 58020, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102357","DOI":"10.1016\/j.arr.2024.102357","article-title":"Neurodegenerative Disorders: Mechanisms of Degeneration and Therapeutic Approaches with Their Clinical Relevance","volume":"99","author":"Gadhave","year":"2024","journal-title":"Ageing Res. 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