{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:19:20Z","timestamp":1787901560376,"version":"build-2784847793"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, where oxidative stress and neuronal apoptosis are key pathogenic events. In this study, we identified a downregulated TRIM2 in the substantia nigra pars compacta (SNc) of PD rats based on label\u2010free proteomics. However, the impact of TRIM2 on PD is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used 6\u2010hydroxydopamine (6\u2010OHDA) to construct a PD model in\u00a0vivo and in\u00a0vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TRIM2 overexpression alleviated neurobehavioral deficits, mitigated the loss of dopaminergic neurons, and suppressed oxidative stress and apoptosis in the SNc of PD rats. These effects were also observed in the 6\u2010OHDA\u2010treated differentiated BE (2)\u2010M17 cells. Mechanistically, the RNA\u2010binding protein ELAVL1 was identified as a critical downstream target, given that the database predicts it to be a TRIM2\u2010interacted protein and a PD\u2010related protein. Herein, TRIM2 directly interacted with ELAVL1 and promoted its ubiquitin\u2010mediated degradation. Crucially, rescue experiments confirmed that the neuroprotection conferred by TRIM2 was counteracted by ELAVL1 overexpression in the 6\u2010OHDA\u2010treated BE (2)\u2010M17 cells that exhibited neuronal\u2010like properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings uncovered a novel TRIM2\u2010ELAVL1 axis as a pivotal regulatory mechanism in PD pathogenesis, positioning TRIM2 as a potential target for therapeutic intervention in PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71075","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:33:31Z","timestamp":1786552411000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Role of\n                    <scp>E3<\/scp>\n                    Ubiquitin Ligase\n                    <scp>TRIM2<\/scp>\n                    in Parkinson's Disease: Attenuation of Oxidative Stress and Apoptosis via Promoting\n                    <scp>ELAVL1<\/scp>\n                    Ubiquitination"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8096-8059","authenticated-orcid":false,"given":"Wei","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WenJie","family":"Sun","sequence":"additional","affiliation":[{"name":"Traditional Chinese Medicine Integrated Department of Nephrology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZhiJun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinYing","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61393-3"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.035980"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.300980"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm6110100"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CS00148A"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bse0410015"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01394-8"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01804-12"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3139"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.220098"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.17065"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071734"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802261105"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06971.x"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt149"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104845"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.197707"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.3378"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01452-3"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1427.036"},{"issue":"11","key":"e_1_2_13_22_1","article-title":"NRF2 Activation and Downstream Effects: Focus on Parkinson's Disease and Brain Angiotensin","volume":"10","author":"Parga J. 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