{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:04:48Z","timestamp":1791867888809,"version":"4.3.4"},"reference-count":111,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170299"],"award-info":[{"award-number":["82170299"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>\u03b1-Lipoic acid (ALA) is a naturally occurring compound with diverse biological functions, widely distributed in animal and plant tissues. It has attracted considerable attention due to its versatile therapeutic potential. However, despite these promising prospects, the clinical application of ALA remains limited by its low bioavailability and chemical instability and an incomplete understanding of its multifaceted mechanisms across various diseases. This review provides a comprehensive overview of the biochemical properties of ALA, including its direct free-radical-scavenging activity, regeneration of endogenous antioxidants, chelation of metal ions, and modulation of inflammatory responses. We also highlight the current evidence regarding ALA\u2019s therapeutic roles and efficacy in major diseases, such as neurodegenerative disorders, lung diseases, cardiovascular diseases, and diabetes. Furthermore, recent advancements and innovative strategies in ALA-based derivatives and drug-delivery systems are summarized, emphasizing their potential to address complex diseases and the necessity for further translational studies. This review aims to provide a theoretical foundation for the rational design of ALA-based therapies, thereby supporting future clinical applications and the optimization of therapeutic strategies.<\/jats:p>","DOI":"10.3390\/molecules30091972","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"1972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Advances in \u03b1-Lipoic Acid for Disease Prevention: Mechanisms and Therapeutic Insights"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0060-9331","authenticated-orcid":false,"given":"Yonglian","family":"Wang","sequence":"first","affiliation":[{"name":"Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5881-4777","authenticated-orcid":false,"given":"Shuxia","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5878-6711","authenticated-orcid":false,"given":"Yaoxuan","family":"He","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4143-3411","authenticated-orcid":false,"given":"Ping","family":"Pang","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6836-2804","authenticated-orcid":false,"given":"Hongli","family":"Shan","sequence":"additional","affiliation":[{"name":"Shanghai Frontiers Science Research Center for Druggability of Cardiovascular Noncoding RNA, Institute for Frontier Medical Technology, School of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai 201620, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1126\/science.114.2952.93","article-title":"Crystalline Alpha-Lipoic Acid; a Catalytic Agent Associated with Pyruvate Dehydrogenase","volume":"114","author":"Reed","year":"1951","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"36346","DOI":"10.1039\/D3RA07140E","article-title":"A-Lipoic Acid Chemistry: The Past 70 Years","volume":"13","author":"Wang","year":"2023","journal-title":"RSC Adv."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3892\/etm.2021.10666","article-title":"Benefits of \u03b1-Lipoic Acid in High-Risk Pregnancies (Review)","volume":"22","author":"Petca","year":"2021","journal-title":"Exp. 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