{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:32:50Z","timestamp":1787502770409,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"39","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373851"],"award-info":[{"award-number":["82373851"]}],"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":["82273906"],"award-info":[{"award-number":["82273906"]}],"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":["82173797"],"award-info":[{"award-number":["82173797"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFE0108600"],"award-info":[{"award-number":["2022YFE0108600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021ZD0202900"],"award-info":[{"award-number":["2021ZD0202900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The spread or transmission of pathologic \u03b1\u2010synuclein (\u03b1\u2010Syn) is emerging as potentially important driver of Parkinson's disease (PD) pathogenesis. Emerging evidence suggests that astrocytes play an important role in uptake\/clearance of extracellular \u03b1\u2010Syn. However, underlying mechanisms and molecular entities responsible for uptake\/clearance of extracellular \u03b1\u2010Syn by astrocytes are not known. Here, it is shown that lipocalin\u20102 (LCN2) is upregulated in astrocytes of MPTP\u2010treated mice by RNA\u2010Seq analysis and positively correlates with pathologic \u03b1\u2010Syn level in \u03b1\u2010Syn PFF model. Strikingly, deletion of astrocytic LCN2 significantly prevents the pathologic \u03b1\u2010Syn accumulation and neurodegeneration. Moreover, 24p3R as a crucial receptor of \u03b1\u2010Syn uptake by astrocytes is identified, as well as an important mediator of \u03b1\u2010Syn spread in the brain. 24p3R specifically binds to \u03b1\u2010Syn and then mediates \u03b1\u2010Syn uptake. LCN2 prevents astrocytic uptake of \u03b1\u2010Syn by impeding the binding of 24p3R and \u03b1\u2010Syn. The identification of LCN2\/24p3R as a key regulator of \u03b1\u2010Syn by astrocytes provides a new target for the treatment of PD and related \u03b1\u2010synucleinopathies.<\/jats:p>","DOI":"10.1002\/advs.202501694","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:00:36Z","timestamp":1753092036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Extracellular LCN2 Binding to 24p3R in Astrocytes Impedes \u03b1\u2010Synuclein Endocytosis in Parkinson's Disease"],"prefix":"10.1002","volume":"12","author":[{"given":"Ying\u2010Ying","family":"Jiao","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"},{"name":"Changzhou Second People's Hospital, Changzhou Medical Center Nanjing Medical University  Changzhou 213000 P. R. China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Nanjing University of Chinese Medicine Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010An","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010Zhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Nanjing Medical University  Nanjing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine The First Affiliated Hospital of Nanjing Medical University  Nanjing 210029 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Wei","family":"Yun","sequence":"additional","affiliation":[{"name":"Changzhou Second People's Hospital, Changzhou Medical Center Nanjing Medical University  Changzhou 213000 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Mei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u2010Hong","family":"Du","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-8389","authenticated-orcid":false,"given":"Ming","family":"Lu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology Nanjing Medical University  Nanjing 211166 P. R. China"},{"name":"Changzhou Second People's Hospital, Changzhou Medical Center Nanjing Medical University  Changzhou 213000 P. R. China"},{"name":"State Key Laboratory of Pharmaceutical Biotechnology Nanjing University  Nanjing 210023 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-023-01216-y"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah3374"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom12050655"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-022-00560-w"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2022.167930"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25767-1"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23920"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202108435"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2110746119"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0954-20.2020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2180202"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2062887"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47266-9"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14373-2"},{"key":"e_1_2_9_9_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28777-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.027"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.308296"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/17618"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abk0637"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01478-2"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15674"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32625-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105696"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201366"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201591397"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28774"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301903"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad298"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2534"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02819-5"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2015.04.009"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.05.015"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00613-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900494"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-021-00562-6"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-024-00703-1"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1871-20.2020"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24245"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03072-0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710442114"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.07.009"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01791-8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.04.003"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI164637"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202357101"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14788-x"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202501694","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202501694","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202501694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T19:06:07Z","timestamp":1773083167000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202501694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":47,"journal-issue":{"issue":"39","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/advs.202501694"],"URL":"https:\/\/doi.org\/10.1002\/advs.202501694","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,21]]},"assertion":[{"value":"2025-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01694"}}