{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T18:32:45Z","timestamp":1774895565822,"version":"3.50.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues on nuclear and cytoplasmic proteins. The identity of O-GlcNAcylated proteins during ageing and neurodegenerative disease remains incompletely defined. Thus, animal models play a crucial role for the systematic characterization and cataloguing of O-GlcNAc-modified proteins. In this study, proteomic analysis was performed to identify O-GlcNAc-modified proteins in both L1 larval and adult stages of wild-type N2 and of\n                    <jats:italic>aex-3<\/jats:italic>\n                    p::Tau(V337M) transgenic\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , a nematode model of ageing and Alzheimer\u2019s disease (AD) using high-resolution nano-LC\u2013ESI mass spectrometry. O-GlcNAcylated proteins identified in the N2 strain were mapped to nuclear- and RNA-related processes in both stages. In the tau-expressing strain, functional enrichment analysis of the identified proteins indicated a predominance of stress-response\u2013related pathways. Together, these data present an analysis of O-GlcNAc-modified proteins across early development, adulthood, and a tau-related\n                    <jats:italic>C. elegans<\/jats:italic>\n                    model, providing a resource for future functional and comparative studies of O-GlcNAcylation in ageing and AD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0344865","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T17:44:03Z","timestamp":1774892643000},"page":"e0344865","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteome-based investigation of O-GlcNAcylation in a C. elegans model of ageing and Alzheimer\u2019s disease: Functional support for earlier hypothesis-generating findings"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3567-9984","authenticated-orcid":true,"given":"Fernando","family":"Garcia Olivera","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"pone.0344865.ref001","unstructured":"World Health Organization. Global action plan on the public health response to dementia 2017-2025. Internet. Publications. WHO. Geneva, 2017. 2025 Sep 24. https:\/\/www.who.int\/publications\/i\/item\/9789241513487"},{"issue":"1","key":"pone.0344865.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/14737175.2019.1540932","article-title":"Therapeutic potential of rescuing protein O-GlcNAcylation in tau-related pathologies","volume":"19","author":"F Di Domenico","year":"2019","journal-title":"Expert Rev Neurother"},{"issue":"5","key":"pone.0344865.ref003","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1111\/jcmm.12807","article-title":"O-GlcNAcylation: a bridge between glucose and cell differentiation","volume":"20","author":"C Sun","year":"2016","journal-title":"J Cell Mol Med"},{"key":"pone.0344865.ref004","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.brainresbull.2020.01.006","article-title":"Chronic hyperglycemia induces tau hyperphosphorylation by downregulating OGT-involved O-GlcNAcylation in vivo and in vitro","volume":"156","author":"R Huang","year":"2020","journal-title":"Brain Res Bull"},{"key":"pone.0344865.ref005","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.brainresbull.2016.08.002","article-title":"O-GlcNAcylation and neurodegeneration","volume":"133","author":"WY Wani","year":"2017","journal-title":"Brain Res Bull"},{"key":"pone.0344865.ref006","doi-asserted-by":"crossref","first-page":"920727","DOI":"10.3389\/fmolb.2022.920727","article-title":"Mapping the O-GlcNAc Modified Proteome: Applications for Health and Disease","volume":"9","author":"RA Burt","year":"2022","journal-title":"Front Mol Biosci"},{"issue":"8","key":"pone.0344865.ref007","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.celrep.2018.07.078","article-title":"O-GlcNAc Signaling Orchestrates the Regenerative Response to Neuronal Injury in Caenorhabditis elegans","volume":"24","author":"DG Taub","year":"2018","journal-title":"Cell Rep"},{"issue":"10","key":"pone.0344865.ref008","article-title":"The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress","volume":"16","author":"SJ Urso","year":"2020","journal-title":"PLoS Genet"},{"issue":"7","key":"pone.0344865.ref009","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/ncb3562","article-title":"O-GlcNAcylation of fumarase maintains tumour growth under glucose deficiency","volume":"19","author":"T Wang","year":"2017","journal-title":"Nat Cell Biol"},{"issue":"9","key":"pone.0344865.ref010","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.1601576","article-title":"Interplay between protein glycosylation pathways in Alzheimer\u2019s disease","volume":"3","author":"M Frenkel-Pinter","year":"2017","journal-title":"Sci Adv"},{"issue":"4","key":"pone.0344865.ref011","article-title":"Discovery and clinical translation of ceperognastat, an O-GlcNAcase (OGA) inhibitor, for the treatment of Alzheimer\u2019s disease","volume":"10","author":"W Kielbasa","year":"2024","journal-title":"Alzheimers Dement (N Y)"},{"issue":"5","key":"pone.0344865.ref012","doi-asserted-by":"crossref","first-page":"3751","DOI":"10.1007\/s12035-018-1326-z","article-title":"Suppressing Tau Aggregation and Toxicity by an Anti-Aggregant Tau Fragment","volume":"56","author":"GJ Pir","year":"2019","journal-title":"Mol Neurobiol"},{"issue":"1","key":"pone.0344865.ref013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.xpro.2020.100276","article-title":"Liquid-culture protocols for synchronous starvation, growth, dauer formation, and dietary restriction of Caenorhabditis elegans","volume":"2","author":"JD Hibshman","year":"2021","journal-title":"STAR Protocols"},{"key":"pone.0344865.ref014","doi-asserted-by":"crossref","first-page":"106289","DOI":"10.1016\/j.biocel.2022.106289","article-title":"An overview of tools to decipher O-GlcNAcylation from historical approaches to new insights","volume":"151","author":"T Dupas","year":"2022","journal-title":"Int J Biochem Cell Biol"},{"issue":"485","key":"pone.0344865.ref015","first-page":"1","article-title":"Identification of Toxoplasma gondii\u2019s O-GlcNAcylated Proteins","volume":"16","author":"M Kupferschmid","year":"2017","journal-title":"Malaria J"},{"issue":"5","key":"pone.0344865.ref016","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1097\/HEP.0000000000000993","article-title":"Tumor suppressive role of the antimicrobial lectin REG3A targeting the O -GlcNAc glycosylation pathway","volume":"81","author":"N Moniaux","year":"2025","journal-title":"Hepatology"},{"issue":"10","key":"pone.0344865.ref017","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202400551RR","article-title":"Complexity and modification of the bull sperm glycocalyx during epididymal maturation","volume":"38","author":"P Se\u010dov\u00e1","year":"2024","journal-title":"FASEB J"},{"issue":"7","key":"pone.0344865.ref018","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0180714","article-title":"WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins","volume":"12","author":"Y Kubota","year":"2017","journal-title":"PLoS One"},{"issue":"1","key":"pone.0344865.ref019","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1038\/s41467-024-47048-3","article-title":"The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation","volume":"15","author":"X Tang","year":"2024","journal-title":"Nat Commun"},{"key":"pone.0344865.ref020","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-981-97-4864-8_2","article-title":"Profiling O-GlcNAcylation with Mass Spectrometry.","volume-title":"Chemistry and Biology of O-GlcNAcylation","author":"Y Zhang","year":"2024"},{"issue":"3","key":"pone.0344865.ref021","doi-asserted-by":"crossref","first-page":"101622","DOI":"10.1016\/j.jbc.2022.101622","article-title":"New insights into the type A glycan modification of Clostridioides difficile flagellar protein flagellin C by phosphoproteomics analysis","volume":"298","author":"PJ Hensbergen","year":"2022","journal-title":"J Biol Chem"},{"issue":"6","key":"pone.0344865.ref022","doi-asserted-by":"crossref","DOI":"10.1128\/jb.00093-23","article-title":"Characterization of the O-Glycoproteome of Flavobacterium johnsoniae","volume":"205","author":"PD Veith","year":"2023","journal-title":"J Bacteriol"},{"key":"pone.0344865.ref023","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkaf394","article-title":"The UniProt website API: facilitating programmatic access to protein knowledge","volume":"53","author":"S Ahmad","year":"2025","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"pone.0344865.ref024","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1534\/genetics.118.301307","article-title":"OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis elegans Genes","volume":"210","author":"W Kim","year":"2018","journal-title":"Genetics"},{"key":"pone.0344865.ref025","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fbioe.2020.00034","article-title":"A Guide to Conquer the Biological Network Era Using Graph Theory","volume":"8","author":"M Koutrouli","year":"2020","journal-title":"Front Bioeng Biotechnol"},{"key":"pone.0344865.ref026","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"D Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"pone.0344865.ref027","doi-asserted-by":"crossref","first-page":"101888","DOI":"10.1016\/j.redox.2021.101888","article-title":"The glyco-redox interplay: Principles and consequences on the role of reactive oxygen species during protein glycosylation","volume":"42","author":"F Khoder-Agha","year":"2021","journal-title":"Redox Biol"},{"issue":"21","key":"pone.0344865.ref028","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.3390\/cells11213509","article-title":"Integration of O-GlcNAc into Stress Response Pathways","volume":"11","author":"KMM Fahie","year":"2022","journal-title":"Cells"},{"issue":"2","key":"pone.0344865.ref029","doi-asserted-by":"crossref","DOI":"10.1093\/g3journal\/jkab013","article-title":"KH domain containing RNA-binding proteins coordinate with microRNAs to regulate Caenorhabditis elegans development","volume":"11","author":"D Haskell","year":"2021","journal-title":"G3 (Bethesda)"},{"issue":"13","key":"pone.0344865.ref030","doi-asserted-by":"crossref","first-page":"20612","DOI":"10.18632\/oncotarget.15296","article-title":"Lipid and Alzheimer\u2019s disease genes associated with healthy aging and longevity in healthy oldest-old","volume":"8","author":"LC Tindale","year":"2017","journal-title":"Oncotarget"},{"key":"pone.0344865.ref031","doi-asserted-by":"crossref","first-page":"1387197","DOI":"10.3389\/fimmu.2024.1387197","article-title":"O-GlcNAc transferase regulates collagen deposition and fibrosis resolution in idiopathic pulmonary fibrosis","volume":"15","author":"S Vang","year":"2024","journal-title":"Front Immunol"},{"key":"pone.0344865.ref032","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1089\/ars.2024.0561","article-title":"Modulation of Protein Disulfide Isomerase Functions by Localization: The Example of the Anterior Gradient Family","volume":"41","author":"AS Pierre","year":"2024","journal-title":"Antioxid Redox Signal"},{"issue":"5","key":"pone.0344865.ref033","doi-asserted-by":"crossref","DOI":"10.15252\/embr.202051412","article-title":"Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors","volume":"22","author":"D Sicari","year":"2021","journal-title":"EMBO Rep"},{"key":"pone.0344865.ref034","doi-asserted-by":"crossref","unstructured":"Liu J-Q, Liu H, Li Y, Liu X, Wang L-Q, Wang K, et al. Protein disulfide isomerase disassembles stress granules and blocks cytoplasmic aggregation of TDP-43 in ALS. Preprint. BioRxiv: 585334.2024. 2025 Sep 24. https:\/\/www.biorxiv.org\/content\/10.1101\/2024.03.16.585334v1","DOI":"10.1101\/2024.03.16.585334"},{"key":"pone.0344865.ref035","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.abb.2016.11.007","article-title":"Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum","volume":"617","author":"AI Soares Moretti","year":"2017","journal-title":"Arch Biochem Biophys"},{"key":"pone.0344865.ref036","doi-asserted-by":"crossref","unstructured":"Holcom A, Fuentealba M, Sivapatham R, King C, Osman H, Foulger A, et al. Neuronal expression of human amyloid-\u03b2 and Tau drives global phenotypic and multiomic changes in C. elegans. Preprint. BioRxiv: 542377.2023. 2025 Sep 24. https:\/\/www.biorxiv.org\/content\/10.1101\/2023.06.01.542377v2","DOI":"10.1101\/2023.06.01.542377"},{"key":"pone.0344865.ref037","unstructured":"Garcia Olivera FC. Tracking of in vivo O-GlcNAcylation in an Alzheimer\u2019s Disease and Aging C. elegans Model. Preprint. 2025. BioRxiv: 659071. 2025 Sep 24. https:\/\/www.biorxiv.org\/content\/10.1101\/2025.07.16.659071v2"},{"issue":"9","key":"pone.0344865.ref038","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.tcb.2024.02.002","article-title":"Metabolic regulation of mRNA splicing","volume":"34","author":"H Cui","year":"2024","journal-title":"Trends Cell Biol"},{"issue":"2","key":"pone.0344865.ref039","article-title":"Tau-Mediated Disruption of the Spliceosome Triggers Cryptic RNA Splicing and Neurodegeneration in Alzheimer\u2019s Disease","volume":"29","author":"Y-C Hsieh","year":"2019","journal-title":"Cell Rep"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0344865","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T17:44:10Z","timestamp":1774892650000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0344865"}},"subtitle":[],"editor":[{"given":"Ashutosh","family":"Pandey","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0344865","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]}}}