{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:55:00Z","timestamp":1791320100170,"version":"4.3.1"},"reference-count":58,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"7","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,2,14]]},"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder characterized by the progressive accumulation of abnormal \u03b1-synuclein (\u03b1-syn) within dopaminergic neurons in the substantia nigra region of the brain. Despite excessive accumulation of \u03b1-syn being key to the pathogenesis of PD, the mechanisms governing its clearance remain elusive. In this study, we found that the endosomal sorting complex required for transport (ESCRT) system plays a crucial role in capturing and facilitating the degradation of ubiquitinated \u03b1-syn. The E3 ubiquitin ligase Listerin was found to promote K27-linked polyubiquitination of \u03b1-syn, directing it to the endosome for subsequent degradation. We showed that the deletion of the Listerin gene exacerbates the neurodegenerative progression in a mouse model of PD, whereas the overexpression of Listerin effectively mitigates disease progression in PD mice. Consequently, our study reveals a mechanism for \u03b1-syn degradation and identifies Listerin as a promising therapeutic target for the treatment of PD.<\/jats:p>","DOI":"10.1126\/sciadv.adp3672","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T18:58:36Z","timestamp":1739386716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":15,"title":["Listerin promotes \u03b1-synuclein degradation to alleviate Parkinson\u2019s disease through the ESCRT pathway"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9019-0588","authenticated-orcid":true,"given":"Fei","family":"Qin","sequence":"first","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8275-3535","authenticated-orcid":true,"given":"Runyu","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9711-4199","authenticated-orcid":true,"given":"Xuemei","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Yuan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxing","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Dong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4589-5509","authenticated-orcid":true,"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-1711","authenticated-orcid":true,"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8440-2274","authenticated-orcid":true,"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Pathogenic Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4817-5355","authenticated-orcid":true,"given":"Bingyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9365-4497","authenticated-orcid":true,"given":"Chengjiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Infection, Immunity and prevention of Shandong Province &amp; Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University, Jinan, Shandong 250012, P.R. China."},{"name":"Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, P.R. China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30295-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16305-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102147"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199603000-00001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00061-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-021-00542-9"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35081564"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1913904117"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024091"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05319-3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01353-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab103"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0177-4"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg2653"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.129"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.add8910"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37464-2"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111058"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.67"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-020-0465-9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1808-9"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.143"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.020"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4269"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01098-9"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09371"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.01.007"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature22815"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1937897"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3406"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3739"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00448-5"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2831-7_6"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2017.09.002"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4474-04.2005"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq290"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401081101"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109356108"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102531"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.529461"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245296"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.12.011"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245321"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aam7787"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16973"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-013118-110729"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.002"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-111315-125249"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812819106"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0118-2"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.3702"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah3374"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3641"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004726"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00917-7"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.add6696"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12111"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adp3672","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T10:31:11Z","timestamp":1744885871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adp3672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":58,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,2,14]]}},"alternative-id":["10.1126\/sciadv.adp3672"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adp3672","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]},"assertion":[{"value":"2024-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadp3672"}}