{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:04:47Z","timestamp":1791867887643,"version":"4.3.4"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2018YFC1603701"],"award-info":[{"award-number":["2018YFC1603701"]}]},{"name":"National Key Research and Development Program of China","award":["81673227"],"award-info":[{"award-number":["81673227"]}]},{"name":"National Key Research and Development Program of China","award":["81001246"],"award-info":[{"award-number":["81001246"]}]},{"name":"National Natural Science Foundation of China","award":["2018YFC1603701"],"award-info":[{"award-number":["2018YFC1603701"]}]},{"name":"National Natural Science Foundation of China","award":["81673227"],"award-info":[{"award-number":["81673227"]}]},{"name":"National Natural Science Foundation of China","award":["81001246"],"award-info":[{"award-number":["81001246"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The prevalence of Alzheimer\u2019s disease (AD) is significantly increasing due to the aging world population, and the currently available drug treatments cannot cure or even slow its progression. \u03b1-lipoic acid (LA) is a biological factor widely found in spinach and meat and can dissolve in both lipid and aqueous phases. In medicine, LA has been shown to reduce the symptoms of diabetic polyneuropathy, acute kidney injury, cancers, and some metabolism-related diseases. This study to proves that \u03b1-lipoic acid (LA) can stabilize the cognitive function of patients with Alzheimer\u2019s disease (AD). BV2 cells were divided into control, LA, A\u03b225\u201335, and LA + A\u03b225\u201335 groups. Cell growth; IL-6, IL-1\u03b2, TNF-\u03b1, IFN-\u03b3, SOD, GPx, CAT, ROS, NO, and iNOS secretion; Wnt-related proteins; cell apoptosis; and cell activation were examined. Here, we found that LA could effectively repress apoptosis and changes in the morphology of microglia BV2 cells activated by A\u03b225\u201335, accompanied by the inhibition of the inflammatory response induced by A\u03b225\u201335. The Wnt\/\u03b2-catenin pathway is also involved in preventing A\u03b225\u201335-induced cytotoxicity in microglia by LA. We found an inhibitory effect of LA on microglia toxicity induced by A\u03b225\u201335, suggesting that a combination of anti-inflammatory and antioxidant substances may offer a promising approach to the treatment of AD.<\/jats:p>","DOI":"10.3390\/molecules28031168","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:23:49Z","timestamp":1674617029000},"page":"1168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Neuroprotective Effect of \u03b1-Lipoic Acid against A\u03b225\u201335-Induced Damage in BV2 Cells"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-9857","authenticated-orcid":false,"given":"Xinrong","family":"Pei","sequence":"first","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyan","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehui","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiya","family":"Luo","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxia","family":"Xing","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Beijing 100052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingxin","family":"Long","sequence":"additional","affiliation":[{"name":"School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jsps.2022.10.004","article-title":"An update on the novel and approved drugs for Alzheimer disease","volume":"30","author":"Hassan","year":"2022","journal-title":"Saudi Pharm. J."},{"key":"ref_2","unstructured":"(2021, February 12). The State of the Art of Dementia Research: New Frontiers. Available online: https:\/\/www.alzint.org\/resource\/world-alzheimer-report-2018\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1111\/jpm.12259","article-title":"A study on knowledge, attitudes and health behaviours regarding Alzheimer\u2019s disease among community residents in Tianjin, China","volume":"22","author":"Yang","year":"2015","journal-title":"J. Psychiatr. Ment. Health Nurs."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1478-811X-12-23","article-title":"Signaling pathway cross talk in Alzheimer\u2019s disease","volume":"12","author":"Godoy","year":"2014","journal-title":"Cell Commun. Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"254954","DOI":"10.1155\/2013\/254954","article-title":"Genetics of Alzheimer\u2019s disease","volume":"2013","author":"Ridge","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.neurol.2014.10.003","article-title":"Amyloid beta peptide immunotherapy in Alzheimer disease","volume":"170","author":"Delrieu","year":"2014","journal-title":"Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.18773\/austprescr.2015.018","article-title":"Treatment for Alzheimer\u2019s disease: Has anything changed?","volume":"38","author":"Waite","year":"2015","journal-title":"Aust. Prescr."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S1734-1140(11)70600-4","article-title":"Lipoic acid\u2014Biological activity and therapeutic potential","volume":"63","author":"Piechota","year":"2011","journal-title":"Pharmacol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1586\/17512433.2014.966816","article-title":"Lipoic acid and lipoic acid analogs in cancer metabolism and chemotherapy","volume":"7","author":"Bingham","year":"2014","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1517\/13543776.2014.937425","article-title":"Therapeutic applications of lipoic acid: A patent review (2011\u20132014)","volume":"24","author":"Koufaki","year":"2014","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/1440-1681.12244","article-title":"\u03b1-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis","volume":"41","author":"Li","year":"2014","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1111\/cbdd.12282","article-title":"Synthesis of new lipoic acid conjugates and evaluation of their free radical scavenging and neuroprotective activities","volume":"83","author":"Bolognesi","year":"2014","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5435","DOI":"10.1016\/j.ejmech.2011.09.001","article-title":"Exploiting the lipoic acid structure in the search for novel multitarget ligands against Alzheimer\u2019s disease","volume":"46","author":"Rosini","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1523\/JNEUROSCI.3751-14.2015","article-title":"Axon initial segment-associated microglia","volume":"35","author":"Baalman","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/glia.22752","article-title":"Reactive retinal microglia, neuronal survival, and the formation of retinal folds and detachments","volume":"63","author":"Fischer","year":"2015","journal-title":"Glia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e91","DOI":"10.1038\/emm.2014.6","article-title":"\u03b21-integrin-dependent migration of microglia in response to neuron-released \u03b1-synuclein","volume":"46","author":"Kim","year":"2014","journal-title":"Exp. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00401-013-1182-x","article-title":"Microglia actions in Alzheimer\u2019s disease","volume":"126","author":"Prokop","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1002\/glia.22654","article-title":"What is microglia neurotoxicity (Not)?","volume":"62","author":"Biber","year":"2014","journal-title":"Glia"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16","DOI":"10.2174\/1389203711314010004","article-title":"Neuron-microglia interaction in neuroinflammation","volume":"14","author":"Suzumura","year":"2013","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3389\/fnagi.2020.00110","article-title":"Microglia and Wnt Pathways: Prospects for Inflammation in Alzheimer\u2019s Disease","volume":"12","author":"Yang","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/glia.21081","article-title":"WNT signaling in activated microglia is proinflammatory","volume":"59","author":"Halleskog","year":"2011","journal-title":"Glia"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1126\/science.1227901","article-title":"Microglia: Scapegoat, saboteur, or something else?","volume":"339","author":"Aguzzi","year":"2013","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/14756366.2012.759951","article-title":"Effects of alpha lipoic acid and its R+ enantiomer supplemented to hyperbaric oxygen therapy on interleukin-6, TNF-\u03b1 and EGF production in chronic leg wound healing","volume":"29","author":"Nasole","year":"2014","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.2174\/1871527312666131223113900","article-title":"Wnt\/\u03b2-catenin signaling in Alzheimer\u2019s disease","volume":"13","author":"Avila","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/cns.12269","article-title":"Wnt signaling pathway, a potential target for Alzheimer\u2019s disease treatment, is activated by a novel multitarget compound ASS234","volume":"20","author":"Ramos","year":"2014","journal-title":"CNS Neurosci. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/clpt.2014.147","article-title":"Longitudinal inflammation, cognitive decline, and Alzheimer\u2019s disease: A mini-review","volume":"96","author":"Bettcher","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/j.1365-2990.2012.01307.x","article-title":"Review: Systemic inflammation and Alzheimer\u2019s disease","volume":"39","author":"Holmes","year":"2013","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.micinf.2015.04.004","article-title":"Infection, systemic inflammation, and Alzheimer\u2019s disease","volume":"17","author":"Lim","year":"2015","journal-title":"Microbes Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"307","DOI":"10.3109\/00207454.2013.833510","article-title":"Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer\u2019s disease","volume":"124","author":"Cai","year":"2014","journal-title":"Int. J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1179\/016164104225016236","article-title":"Nitric oxide pathways in Alzheimer\u2019s disease and other neurodegenerative dementias","volume":"26","author":"Togo","year":"2004","journal-title":"Neurol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3806157","DOI":"10.1155\/2016\/3806157","article-title":"Getting to NO Alzheimer\u2019s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide","volume":"2016","author":"Balez","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.yexcr.2004.02.028","article-title":"Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons","volume":"297","author":"Alvarez","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6545","DOI":"10.1523\/JNEUROSCI.0421-09.2009","article-title":"Interruption of beta-catenin signaling reduces neurogenesis in Alzheimer\u2019s disease","volume":"29","author":"He","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e48328","DOI":"10.15252\/embr.201948328","article-title":"Tau acetylates and stabilizes beta-catenin thereby promoting cell survival","volume":"21","author":"Liu","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_36","first-page":"189","article-title":"Alpha-lipoic acid as a new treatment option for Alzheimer\u2019s disease\u2014A 48 months follow-up analysis","volume":"72","author":"Hager","year":"2007","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_37","first-page":"454253","article-title":"The Effect of Lipoic Acid Therapy on Cognitive Functioning in Patients with Alzheimer\u2019s Disease","volume":"2013","author":"Fava","year":"2013","journal-title":"J. Neurodegener. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.addr.2008.04.015","article-title":"Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer\u2019s disease","volume":"60","author":"Maczurek","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jdiacomp.2009.09.007","article-title":"Role of lipoic acid on insulin resistance and leptin in experimentally diabetic rats","volume":"25","author":"Kandeil","year":"2011","journal-title":"J. Diabetes Complicat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.exger.2009.08.012","article-title":"Short-term supplementation with acetyl-L-carnitine and lipoic acid alters plasma protein carbonyl levels but does not improve cognition in aged beagles","volume":"44","author":"Christie","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1111\/acel.12602","article-title":"Enhanced NOLC1 promotes cell senescence and represses hepatocellular carcinoma cell proliferation by disturbing the organization of nucleolus","volume":"16","author":"Yuan","year":"2017","journal-title":"Aging Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17043","DOI":"10.1038\/cddiscovery.2017.43","article-title":"Nucleolar and coiled-body phosphoprotein 1 (NOLC1) regulates the nucleolar retention of TRF2","volume":"3","author":"Yuan","year":"2017","journal-title":"Cell Death Discov."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/3\/1168\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:14:58Z","timestamp":1760120098000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/3\/1168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,24]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["molecules28031168"],"URL":"https:\/\/doi.org\/10.3390\/molecules28031168","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,24]]}}}