{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:43:51Z","timestamp":1772160231315,"version":"3.50.1"},"reference-count":58,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31730035"],"award-info":[{"award-number":["31730035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91632305"],"award-info":[{"award-number":["91632305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["9194920041"],"award-info":[{"award-number":["9194920041"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Elevated serum homocysteine (Hcy) level is a risk factor for Alzheimer's disease (AD) and accelerates cell aging. However, the mechanism by which Hcy induces neuronal senescence remains largely unknown. In this study, we observed that Hcy significantly promoted senescence in neuroblastoma 2a (N2a) cells with elevated \u03b2\u2010catenin and Kelch\u2010like ECH\u2010associated protein 1 (KEAP1) levels. Intriguingly, Hcy promoted the interaction between KEAP1 and the Wilms tumor gene on the X chromosome (WTX) while hampering the \u03b2\u2010catenin\u2010WTX interaction. Mechanistically, Hcy attenuated the methylation level of the KEAP1 promoter CpG island and activated KEAP1 transcription. However, a slow degradation rate rather than transcriptional activation contributed to the high level of \u03b2\u2010catenin. Hcy\u2010upregulated KEAP1 competed with \u03b2\u2010catenin to bind to WTX. Knockdown of both \u03b2\u2010catenin and KEAP1 attenuated Hcy\u2010induced senescence in N2a cells. Our data highlight a crucial role of the KEAP1\u2010\u03b2\u2010catenin pathway in Hcy\u2010induced neuronal\u2010like senescence and uncover a promising target for AD treatment.<\/jats:p>","DOI":"10.1111\/ejn.16318","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T07:04:13Z","timestamp":1710831853000},"page":"2732-2747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Homocysteine\u2010potentiated Kelch\u2010like ECH\u2010associated protein 1 promotes senescence of neuroblastoma 2a cells via inhibiting ubiquitination of \u03b2\u2010catenin"],"prefix":"10.1111","volume":"59","author":[{"given":"Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"Endocrine Department of Liyuan Hospital; Key Laboratory of Ministry of Education of China for Neurological Disorders, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Zhao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China\/Hubei Province for Neurological Disorders, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Precision Medical Center, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College Huazhong University of Science &amp; Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Endocrine Department of Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao\u2010Juan","family":"Yang","sequence":"additional","affiliation":[{"name":"Endocrine Department of Liyuan Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China\/Hubei Province for Neurological Disorders, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China\/Hubei Province for Neurological Disorders, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China\/Hubei Province for Neurological Disorders, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"},{"name":"Co\u2010innovation Center of Neuroregeneration Nantong University  Nantong China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI95145"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2012.01.004"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144090"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-03465-6"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370220949237"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.067512"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2009.06.017"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2014.09.018"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0505-1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-014-1338-7"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527312666131223113900"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-021-00142-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9090904"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.153.5.1049"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.001438"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-12-4400"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200205115"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13071"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.150"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0525-5"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.10.018"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2012.00870.x"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5612"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2016.04.008"},{"issue":"3","key":"e_1_2_11_26_1","first-page":"467","article-title":"DNA hypomethylation at the CpG island is involved in aberrant expression of the L1 cell adhesion molecule gene in colorectal cancer","volume":"35","author":"Kato K.","year":"2009","journal-title":"International Journal of Oncology"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(93)90250-L"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-18-06920.2000"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.198"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143578"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science\/1141515"},{"issue":"4","key":"e_1_2_11_32_1","first-page":"126","article-title":"Homocysteine and Alzheimer's disease","volume":"57","author":"Miller J. W.","year":"1999","journal-title":"Nutrition Reviews"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102181"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10525"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12840"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.10.010"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6882-13-261"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.15.1837"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03319"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1068"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8281-1"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/life12091332"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.7762\/cnr.2016.5.1.7"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2019.109394"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01991-06"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.11.004"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2007.01.001"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01278-3"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2022.102284"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054265"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53225-y"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-012-1498-1"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303899"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2007.04.015"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081036"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.08.029"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-00336-7"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.01.011"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.16318","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T08:44:25Z","timestamp":1716281065000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.16318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":58,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/ejn.16318"],"URL":"https:\/\/doi.org\/10.1111\/ejn.16318","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/EJN.16318\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/EJN.16318\/v1\/decision1","asserted-by":"object"}]},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,19]]},"assertion":[{"value":"2023-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}