{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:14:57Z","timestamp":1778220897837,"version":"3.51.4"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      p53 plays a critical role in Parkinson's disease (PD) pathogenesis. p53 activation induces mitochondrial dysfunction and reactive oxygen species (ROS) production, contributing to progressive dopaminergic neuron degeneration. Although \u03b1-lipoic acid (ALA) exhibits neuroprotective effects in neurodegeneration, its underlying mechanisms remain unclear. This study investigated the neuroprotective role and molecular mechanism of ALA in 1-methyl-4-phenylpyridinium (MPP\n                      <jats:sup>+<\/jats:sup>\n                      )- treated PC12 cells, a cellular model of dopaminergic toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Neuroprotective effects of ALA on dopaminergic neurons were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell viability, Hoechst 33258 staining and flow cytometry to detect cellular apoptosis, and western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ALA treatment significantly inhibited p53 expression and attenuated MPP\n                      <jats:sup>+<\/jats:sup>\n                      -induced apoptosis in dopaminergic neurons. ALA also prevented annexin A2 degradation and protected PC12 cells from MPP\n                      <jats:sup>+<\/jats:sup>\n                      -induced toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ALA downregulates p53 expression by preventing annexin A2 degradation, thereby reducing p53 protein levels and providing neuroprotection under neurodegenerative conditions. This suggests the potential of ALA in modulating p53 pathways for PD therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1837965","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:51:11Z","timestamp":1778219471000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Lipoic acid suppresses p53 by preventing annexin A2 degradation to protect dopaminergic neurons in a Parkinson's disease model"],"prefix":"10.3389","volume":"20","author":[{"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"Department of General Practice, Songjiang Hospital Affiliated Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WenPing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of General Practice, Songjiang Hospital Affiliated Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"a000935","DOI":"10.1101\/cshperspect.a000935","article-title":"Transcriptional regulation by p53","volume":"2","author":"Beckerman","year":"2010","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.31083\/j.fbl2901036","article-title":"Significance of mitochondrial dysfunction in the pathogenesis of Parkinson's disease","volume":"29","author":"Blagov","year":"2024","journal-title":"Front. Biosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"20702","DOI":"10.18632\/aging.103998","article-title":"Stress-induced p53 drives BAG5 cochaperone expression to control alpha-synuclein aggregation in Parkinson's disease","volume":"12","author":"Chen","year":"2020","journal-title":"Aging"},{"key":"B4","doi-asserted-by":"publisher","first-page":"10645","DOI":"10.2147\/DDDT.S522381","article-title":"Exploratory study on the role of emodin in alleviating MPTP-induced neurotoxicity: a focus on p53-ferroptosis signaling","volume":"19","author":"Chen","year":"2025","journal-title":"Drug Des. Devel. Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s13024-016-0079-2","article-title":"Costa C: direct alpha-synuclein promoter transactivation by the tumor suppressor p53","volume":"11","author":"Duplan","year":"2016","journal-title":"Mol. Neurodegener."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1817","DOI":"10.3892\/ijmm.2018.3406","article-title":"Damage to dopaminergic neurons by oxidative stress in Parkinson's disease (Review)","volume":"41","author":"Guo","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"406273","DOI":"10.1155\/2012\/406273","article-title":"The annexin A2\/S100A10 system in health and disease: emerging paradigms","volume":"2012","author":"Hedhli","year":"2012","journal-title":"J. Biomed. Biotechnol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/s41593-022-01061-1","article-title":"Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson's disease","volume":"25","author":"Kamath","year":"2022","journal-title":"Nat. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3671","DOI":"10.1016\/j.cell.2024.05.030","article-title":"TNF-NF-kappaB-p53 axis restricts in vivo survival of hPSC-derived dopamine neurons","volume":"187","author":"Kim","year":"2024","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3892\/ijmm.2013.1361","article-title":"alpha-lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation","volume":"32","author":"Li","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1097\/WNR.0000000000001721","article-title":"Annexin A2 degradation contributes to dopaminergic cell apoptosis via regulating p53 in neurodegenerative conditions","volume":"32","author":"Li","year":"2021","journal-title":"Neuroreport"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4360","DOI":"10.3892\/mmr.2016.5754","article-title":"alpha-lipoic acid exerts neuroprotective effects on neuronal cells by upregulating the expression of PCNA via the P53 pathway in neurodegenerative conditions","volume":"14","author":"Li","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"103787","DOI":"10.1016\/j.redox.2025.103787","article-title":"Decoding Parkinson's disease: the interplay of cell death pathways, oxidative stress, and therapeutic innovations","volume":"85","author":"Liu","year":"2025","journal-title":"Redox Biol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"6039769","DOI":"10.1155\/2020\/6039769","article-title":"Functional role of p53 in the regulation of chemical-induced oxidative stress","volume":"2020","author":"Liu","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1111\/bph.12978","article-title":"Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation","volume":"172","author":"Liu","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"6600944","DOI":"10.1155\/2022\/6600944","article-title":"Association of p53 with neurodegeneration in Parkinson's disease","volume":"2022","author":"Luo","year":"2022","journal-title":"Parkinson's Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.neulet.2006.12.003","article-title":"p53 protein, interferon-gamma, and NF-kappaB levels are elevated in the parkinsonian brain","volume":"414","author":"Mogi","year":"2007","journal-title":"Neurosci. Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1715","DOI":"10.1089\/ars.2010.3499","article-title":"Role of MnSOD and p66shc in mitochondrial response to p53","volume":"15","author":"Pani","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"B19","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.lfs.2019.03.057","article-title":"Parkinson's disease: mechanisms, translational models and management strategies","volume":"226","author":"Raza","year":"2019","journal-title":"Life Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ijbiomac.2021.01.042","article-title":"Tantalizing role of p53 molecular pathways and its coherent medications in neurodegenerative diseases","volume":"172","author":"Talebi","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1016\/j.cell.2012.05.014","article-title":"p53 opens the mitochondrial permeability transition pore to trigger necrosis","volume":"149","author":"Vaseva","year":"2012","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"32512","DOI":"10.1074\/jbc.M112.351957","article-title":"Annexin A2 silencing induces G2 arrest of non-small cell lung cancer cells through p53-dependent and -independent mechanisms","volume":"287","author":"Wang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1080\/00207454.2022.2158824","article-title":"Implications of p53 in mitochondrial dysfunction and Parkinson's disease","volume":"134","author":"Wang","year":"2024","journal-title":"Int. J. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.7150\/jca.29440","article-title":"Annexin A2 silencing inhibits proliferation and epithelial-to-mesenchymal transition through p53-dependent pathway in NSCLCs","volume":"10","author":"Wu","year":"2019","journal-title":"J. Cancer"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3745","DOI":"10.1158\/0008-5472.CAN-04-3835","article-title":"p53 translocation to mitochondria precedes its nuclear translocation and targets mitochondrial oxidative defense protein-manganese superoxide dismutase","volume":"65","author":"Zhao","year":"2005","journal-title":"Cancer Res."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1837965\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:51:12Z","timestamp":1778219472000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1837965\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":25,"alternative-id":["10.3389\/fnins.2026.1837965"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1837965","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1837965"}}