{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:35:45Z","timestamp":1762432545699,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Parkinson's disease (PD) is a neurodegenerative disorder characterised by pyroptosis. O\u2010GlcNAcylation, regulated solely by O\u2010GlcNAc transferase (OGT) and O\u2010GlcNAcase (OGA), has been shown to mitigate PD. This study aimed to investigate whether pyroptosis and PD pathogenesis are modulated by O\u2010GlcNAcylation. In PD model cells, O\u2010GlcNAc protein levels were downregulated, while OGA expression was upregulated. Knockdown of OGA significantly protected BV2 cells from LPS\u2010induced injury by inhibiting pyroptosis. Inhibition of OGA notably increased the O\u2010GlcNAc levels of NEK7. Furthermore, O\u2010GlcNAcylated NEK7 protein levels were significantly reduced by mutations at T170 or T172, whereas phosphorylated NEK7 protein levels were downregulated only by mutations at T172. Co\u2010immunoprecipitation (co\u2010IP) confirmed the endogenous interaction between NEK7 and NLRP3, which was weakened by OGA knockdown. In animal experiments, OGA deficiency significantly reduced motor dysfunctions and dopaminergic neurodegeneration in MPTP\u2010treated mice. OGT deficiency abolished the protective effects of OGA knockdown against MPTP\u2010induced injury. Additionally, OGT inhibition in OGA knockdown mice promoted pyroptosis. Collectively, these findings indicate that high OGA levels decrease O\u2010GlcNAcylation in PD, thereby promoting pyroptosis via the activation of the NEK7\/NLRP3 pathway.<\/jats:p>","DOI":"10.1111\/jcmm.70874","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:59:13Z","timestamp":1760032753000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["O\u2010<scp>GlcNAcylation<\/scp> Mediated by <scp>OGA<\/scp> Activates <scp>NEK7<\/scp>\/<scp>NLRP3<\/scp> Pathway to Promote Pyroptosis in Parkinson's Disease"],"prefix":"10.1111","volume":"29","author":[{"given":"Zhi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6671-8436","authenticated-orcid":false,"given":"Ying","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Harbin Medical University  Harbin China"},{"name":"Key Laboratory of Hepatosplenic Surgery, Ministry of Education The First Affiliated Hospital of Harbin Medical University  Harbin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2157-1"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14411"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2019.03.001"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03713-0"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.03.038"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00886-5"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102340"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-13601-8"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-020-00505-0"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa320"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0403471101"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.719807"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.12.019"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1295-z"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2011.128"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02755-4"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1141-5"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168888"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105197"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.02.005"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1155630"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.96"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-018-0124-5"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.108977"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.607080"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103215"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050421"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808845116"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00709-5"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11030648"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201810248"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.108963"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102134"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-00893-0"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512202"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01107-9"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-42813-8"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70874","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T14:00:55Z","timestamp":1760450455000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":37,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/jcmm.70874"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70874","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"type":"print","value":"1582-1838"},{"type":"electronic","value":"1582-4934"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70874"}}