{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T23:41:51Z","timestamp":1761176511802,"version":"build-2065373602"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360386"],"award-info":[{"award-number":["82360386"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>NACHT, LRR, and PYD domains\u2010containing protein 3 (NLRP3) inflammasome plays a pivotal role in the progression of cerebral ischemia\/reperfusion injury (CI\/RI). We aimed to investigate the implication of WW domain\u2010containing protein 2 (WWP2), an E3 ubiquitin ligase, in CI\/RI and its mechanism. Microglia were subjected to oxygen\u2013glucose deprivation\/reoxygenation, and mice were subjected to middle cerebral artery occlusion (MCAO) for modeling. WWP2 was reduced in the brain tissues of mice with MCAO\/R. WWP2 overexpression in microglia inhibited the NLRP3 inflammasome activation to alleviate MCAO\/R\u2010induced injury and microglia\u2010induced neurotoxicity. WWP2 inhibited the mitochondrial translocation of NLRP3 by degrading mitochondrial antiviral\u2010signaling protein (MAVS) to block its interaction with NLRP3, and MAVS overexpression in microglia promoted the NLRP3 activation to exacerbate MCAO\/R and neurotoxicity. The nuclear export of TAR DNA\u2010binding protein 43 (TDP\u201043) in MCAO\/R promoted the WWP2 degradation via the (UG)n element of the 3\u2032UTR of WWP2. TDP\u201043 overexpression also impaired the blockade of NLRP3 activation and exacerbated neurotoxicity in the presence of WWP2. Overall, our investigations demonstrate that nuclear export of TDP\u201043 in microglia activates NLRP3 inflammasome and exacerbates CI\/RI by blocking MAVS degradation through (UG)n element\u2010mediated instability of WWP2.<\/jats:p>","DOI":"10.1002\/glia.70077","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T04:19:49Z","timestamp":1754713189000},"page":"2445-2463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>WWP2<\/scp>\n                    Overexpression Represses\n                    <scp>NLRP3<\/scp>\n                    Inflammasome Activation in Cerebral Ischemia\/Reperfusion Injury Through the Degradation of\n                    <scp>MAVS<\/scp>"],"prefix":"10.1002","volume":"73","author":[{"given":"Hang","family":"Yu","sequence":"first","affiliation":[{"name":"Dalian Medical University  Dalian Liaoning People's Republic of China"},{"name":"Cardiovascular Medicine Intensive Care Unit The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghao","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Intensive Care Unit The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Lu","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Intensive Care Unit The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0710-3868","authenticated-orcid":false,"given":"Mingming","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Neurology The Second Affiliated Hospital of Hainan Medical University  Haikou Hainan People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianyao","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Dalian Medical University  Dalian Liaoning People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13161365"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.016"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201051199\u20108"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418\u2010024\u201001376\u20105"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.fbl2902072"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2024.13170"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103244"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011\u2010024\u201001949\u20107"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx175"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010023\u201002931\u2010z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010022\u201000962\u20102"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114671"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2024.101883"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010017\u20100921\u20107"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400687R"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114687"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000608\u20105"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3704"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974\u2010022\u201002421\u20101"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23512"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.054"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/09603271241292165"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010676"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2022.847440"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S350109"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3724\/abbs.2022091"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010022\u201000734\u2010y"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2021.01.030"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010022\u201002869\u20105"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1250918"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.06.015"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2024.101257"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.13970"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.07.019"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.100880"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1046\u20102023(02)00358\u20104"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.70077","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T10:15:56Z","timestamp":1761128156000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.70077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/glia.70077"],"URL":"https:\/\/doi.org\/10.1002\/glia.70077","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"type":"print","value":"0894-1491"},{"type":"electronic","value":"1098-1136"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"assertion":[{"value":"2025-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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