{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T03:07:18Z","timestamp":1782702438335,"version":"3.54.5"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["2022R1C1C1006166"],"award-info":[{"award-number":["2022R1C1C1006166"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["RS\u20102025\u201000558841"],"award-info":[{"award-number":["RS\u20102025\u201000558841"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG087190\u201001A1"],"award-info":[{"award-number":["R01 AG087190\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Netrin\u20101 is stably expressed in mature neurons, where it regulates synaptic plasticity, promotes neuronal survival, and modulates cell adhesion and migration. However, the molecular link between Netrin\u20101 and the pathogenesis of Parkinson's disease (PD) has not yet been clearly elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In this study, we investigated the neuroprotective effects of Netrin\u20101 against dopaminergic neuronal death associated with PD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we show that in a rotenone\u2010induced cellular model, Netrin\u20101 treatment significantly reduced reactive oxygen species (ROS) production, \u03b1\u2010synuclein phosphorylation, and subsequent apoptosis. Moreover, Netrin\u20101 suppressed the expression of pro\u2010inflammatory cytokines, including IL\u20106, TNF\u2010\u03b1, and IL\u20101\u03b2, and promoted the activation of dopamine D2 receptor (DRD2) signaling, which is crucial for dopaminergic neuron survival. Of note, in the Netrin\u20101 conditional knockout mouse model, we observed significant dopaminergic neuronal loss, accompanied by increased \u03b1\u2010synuclein hyperphosphorylation at Ser129 and elevated levels of the truncated form of deleted in colorectal cancer (DCC) generated by activated caspase\u20103, a marked depletion of DRD2 expression, and hyperphosphorylation of GSK3\u03b2 at Tyr216. In contrast, these pathological features were attenuated in Netrin\u20101 wild\u2010type (WT) mice. Additionally, the aging process in \u03b1\u2010synuclein (SNCA) transgenic (Tg) mice was characterized by reduced levels of Netrin\u20101 and DRD2, alongside increased \u03b1\u2010synuclein accumulation, proinflammatory cytokines, and caspase\u20103 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest that Netrin\u20101 protects dopaminergic neurons by regulating neuroinflammation, preserving DRD2 signaling, and inhibiting phosphorylation of GSK3\u03b2 at Tyr216, thereby offering potential as a therapeutic agent for dopaminergic neurodegeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70651","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T04:14:52Z","timestamp":1763439292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Netrin\u20101 Inhibits Neuroinflammation by Modulating\n                    <scp>DRD2<\/scp>\n                    \/\n                    <scp>GSK3\u03b2<\/scp>\n                    Signaling and Suppressing\n                    <scp>ROS<\/scp>\n                    in a Parkinson's Disease Model"],"prefix":"10.1111","volume":"31","author":[{"given":"Lee Ya","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Medicine Hallym University  Chuncheon\u2010si Gangwon\u2010Do South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hoon","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of 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