{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:19:25Z","timestamp":1787901565600,"version":"build-2784847793"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["U24A20691"],"award-info":[{"award-number":["U24A20691"]}],"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":["82271377"],"award-info":[{"award-number":["82271377"]}],"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":["81901229"],"award-info":[{"award-number":["81901229"]}],"id":[{"id":"10.13039\/501100001809","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":["2022B1515120042"],"award-info":[{"award-number":["2022B1515120042"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2025B03J0035"],"award-info":[{"award-number":["2025B03J0035"]}],"id":[{"id":"10.13039\/501100010256","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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) is a chronic neuroinflammatory disorder characterized by oligodendrocyte injury and demyelination. The disease progresses from peripheral immune attacks to compartmentalized central nervous system (CNS) inflammation, culminating in irreversible neurodegeneration. Although current immunotherapies suppress peripheral relapses, they inadequately address compartmentalized CNS inflammation and progressive neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reanalyzed published single\u2010nucleus RNA\u2010seq datasets from human MS lesions. Primary astrocytes, oligodendrocytes, and organotypic cultures were used for in\u00a0vitro studies. Outcomes were assessed by immunofluorescence, Western blot, qRT\u2010PCR, RNA\u2010seq, cell viability assay, and behavioral scoring. The STING inhibitor H\u2010151 was administered in preventive and therapeutic paradigms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Single\u2010nucleus RNA\u2010seq showed inflammatory astrocytes accumulate preferentially at chronic active lesion edges in MS. These astrocytes exhibited STING pathway activation, coinciding with elevated DNA concentrations in cerebrospinal fluid. Mechanistically, DNA synergized with pro\u2010inflammatory cytokines to trigger astrocytic STING signaling, driving Clusterin (CLU) secretion that directly induced oligodendrocyte apoptosis and demyelination. Pharmacological inhibition of STING with H\u2010151 prevented and ameliorated established clinical deficits in experimental autoimmune encephalomyelitis mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DNA elevation in inflammatory microenvironments activates the astrocytic STING\u2013CLU axis to promote disease pathogenesis, validating STING targeting as a treatment strategy for MS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71091","type":"journal-article","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T06:35:48Z","timestamp":1786775748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>cGAS<\/scp>\n                    \u2013\n                    <scp>STING<\/scp>\n                    Pathway Drives Astrocyte\u2010Mediated Demyelination in Multiple Sclerosis Through Clusterin Secretion"],"prefix":"10.1002","volume":"32","author":[{"given":"Shengfei","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-4628","authenticated-orcid":false,"given":"Yiying","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shishi","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Neurology Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou 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