{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:18:36Z","timestamp":1788499116466,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515012530"],"award-info":[{"award-number":["2023A1515012530"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515110543"],"award-info":[{"award-number":["2023A1515110543"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471335"],"award-info":[{"award-number":["82471335"]}],"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":["82171307"],"award-info":[{"award-number":["82171307"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Communication between the immune system and the brain is critical for neuronal health, yet the molecular signals that mediate this crosstalk are not fully understood. Here, we uncover an unexpected and direct neuroprotective axis linking the thymus to the central nervous system (CNS). We show that the thymus\u2010derived peptide Thymosin alpha\u20101 (T\u03b11) functions as a non\u2010canonical ligand for the Hypocretin (Orexin) Receptor 1 (HCRTR1), a classical neuropeptide receptor on neurons. This engagement shields neurons from cell death by suppressing the activity of Receptor\u2010Interacting Protein Kinase 3 (RIPK3), a central executioner of necroptosis. The physiological relevance of this pathway is highlighted in ischemic stroke, where we found that circulating T\u03b11 levels were significantly reduced in patients and mice, strongly correlating with disease severity. Genetic deletion of the T\u03b11\u2010encoding gene\n                    <jats:italic>Ptma<\/jats:italic>\n                    exacerbated stroke injury, whereas therapeutic administration of T\u03b11 conferred robust neuroprotection and improved functional recovery. Our findings identify a novel thymus\u2010brain signaling pathway, revealing a new neuroprotective function for an immune peptide and an unexpected role for a canonical neuronal receptor. This work establishes T\u03b11 as a promising dual\u2010action therapeutic candidate, capable of both direct neuronal protection and systemic immunomodulation.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522372","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:54:45Z","timestamp":1788497685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Thymosin Alpha\u20101 Provides Direct Neuroprotection by Engaging the Orexin Receptor HCRTR1 to Suppress Neuronal Necroptosis"],"prefix":"10.1002","author":[{"given":"Xinmei","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liubin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotao","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotong","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0368","authenticated-orcid":false,"given":"Zhengqi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurology Mental and Neurological Disease Research Center the Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Brain Function and Disease  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo7649"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2025.1590002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201007469\u2010y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2025.156974"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.5.1391"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.4.1008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12030496"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13963"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010015\u20109671\u20107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14858"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010019\u201000346\u2010z"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0192\u20100561(00)00065\u20105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079\u2010022\u201000700\u20103"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44321\u2010025\u201000206\u20106"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2022.09.009"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010023\u201003728\u20107"},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","DOI":"10.1002\/mco2.70107","article-title":"Noncanonical Feedback Loop between \u201cRIP3\u2010MLKL\u201d and \u201c4EBP1\u2010eIF4E\u201d Promotes Neuronal Necroptosis","volume":"6","author":"Wang S.","year":"2020","journal-title":"MedComm"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010018\u20100095\u20107"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221149509"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011\u2010011\u20109241\u20102"},{"key":"e_1_2_9_22_1","first-page":"78","article-title":"Brain\u2010Thymus Connections in Chagas Disease","volume":"31","author":"Gonzalez F. 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