{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:45:46Z","timestamp":1787316346574,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82241043"],"award-info":[{"award-number":["82241043"]}],"id":[{"id":"10.13039\/501100001809","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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Myeloid\u2010derived suppressor cells (MDSCs) are elevated in Parkinson's disease (PD), but their functional role remains unclear. This study investigated whether GSDMD deficiency enhances the immunosuppressive activity of granulocytic MDSCs (G\u2010MDSCs) to mitigate PD progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Flow cytometry and Western blot analyzed G\/M\u2010MDSCs in 37 PD patients and 21 controls. An MPTP\u2010induced PD mouse model was used to assess GSDMD\u2010deficient G\u2010MDSCs through behavioral tests, immunohistochemistry, and adoptive transfer experiments. The NLRP3 inhibitor ACT001 was evaluated for therapeutic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PD patients and MPTP\u2010treated mice showed increased peripheral G\u2010MDSCs with reduced NLRP3\/GSDMD activation. GSDMD knockout mice exhibited attenuated PD symptoms, reversed by MDSCs depletion. Adoptive transfer of GSDMD\u2010deficient G\u2010MDSCs suppressed microglial activation and improved motor function. ACT001 enhanced G\u2010MDSCs immunosuppression and alleviated PD pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GSDMD deficiency promotes immunosuppressive G\u2010MDSCs that inhibit neuroinflammation and PD progression. Targeting GSDMD to modulate MDSCs' function represents a novel therapeutic strategy for PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70626","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T06:43:23Z","timestamp":1760424203000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>GSDMD<\/scp>\n                    \u2010Deficient G\u2010\n                    <scp>MDSCs<\/scp>\n                    Exert Profoundly Suppressive Activity to Relieve\n                    <scp>MPTP<\/scp>\n                    \u2010Induced Parkinson's Disease"],"prefix":"10.1111","volume":"31","author":[{"given":"Qi","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Basic Medicine, School of Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8325-0405","authenticated-orcid":false,"given":"Guotao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Affiliated Hospital Yangzhou University, Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Subei People's Hospital Yangzhou University  Yangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijuan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine, School of Medicine Yangzhou University  Yangzhou China"},{"name":"Department of Gastroenterology, Affiliated Hospital Yangzhou University, Yangzhou University  Yangzhou China"},{"name":"Department of Neurology, Affiliated Subei People's Hospital Yangzhou University  Yangzhou China"},{"name":"Univeristy Key Laboratory of Jiangsu Province for Nucleic Acid &amp; 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