{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:24:06Z","timestamp":1786976646575,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014076","name":"Stichting ALS Nederland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017694","name":"Hermann und Lilly Schilling-Stiftung f\u00fcr Medizinische Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017694","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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Recent research demonstrated activation of the innate immune system in ALS models. This pathway can be activated by cGAS\u2010STING sensing of cytosolic DNA that accumulates as a result of chronic DNA damage and defective mitochondria, both of which was identified as pathology in FUS\u2010ALS. Therefore, we analyzed innate immune pathways in FUS\u2010ALS, which revealed upregulation of interferon\u2010stimulated genes (ISGs) and activation of the TBK1\u2010IRF3 pathway in FUS\n                    <jats:sup>mut<\/jats:sup>\n                    iPSC\u2010derived spinal motor neurons (sMNs). Accumulation of cytosolic dsRNA and its sensor RIG\u2010I, but not MDA5, was found to be significantly upregulated in FUS\n                    <jats:sup>mut<\/jats:sup>\n                    sMNs, which was abolished upon siRNA\u2010mediated knockdown of RIG\u2010I. RIG\u2010I was highly expressed in FUS\u2010ALS post\u2010mortem \u03b1\u2010MNs. IFN treatment of FUS\n                    <jats:sup>wt<\/jats:sup>\n                    sMNs phenocopied the axonal degeneration of FUS\n                    <jats:sup>mut<\/jats:sup>\n                    sMNs. Mitochondrial transcription, a known source of dsRNA, was found to be upregulated in compartmental axonal RNAseq analysis and its inhibition reduced ISGs in FUS\u2010ALS sMNs. The JAK\u2010STAT inhibitor ruxolitinib alleviated the upregulated ISG expression and reversed the axonal degeneration of sMNs. Finally, we analyzed ISG expression in peripheral blood from 18 FUS\u2010ALS patients, eight of whom had a significantly elevated interferon signature. RIG\u2010I\u2010mediated innate immune activation in sMNs may be an interesting novel individualized biomarker\u2010driven therapeutic target in (FUS\u2010) ALS.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>A one\u2010sentence summary of your paper<\/jats:bold>\n                    : RIG\u2010I\u2010mediated innate immune activation is found in FUS\u2010ALS spinal motor neurons caused by cytosolic dsRNA accumulation due to mitochondrial transcriptional activation and is amenable to JAK\u2010STAT inhibition and might thus be an interesting novel individualized biomarker\u2010driven therapeutic approach in (FUS\u2010) ALS.\n                  <\/jats:p>","DOI":"10.1002\/advs.202417135","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T10:46:28Z","timestamp":1769597188000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["RIG\u2010I Mediated Neuron\u2010Specific IFN Type 1 Signaling in FUS\u2010ALS Induces Neurodegeneration and Offers New Biomarker\u2010Driven Individualized Treatment Options for (FUS\u2010)ALS"],"prefix":"10.1002","volume":"13","author":[{"given":"Marcel","family":"Naumann","sequence":"first","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d Department of Neurology University Medical Center Rostock University of Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa M.","family":"Wierschin","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d Department of Neurology University Medical Center Rostock University of Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kretschmer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medizinische Fakult\u00e4t Carl Gustav Carus Technische Universit\u00e4t Dresden  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banaja P.","family":"Dash","sequence":"additional","affiliation":[{"name":"Translational Neurodegeneration Section \u201cAlbrecht Kossel\u201d Department of Neurology University Medical Center Rostock University of Rostock  Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Held","sequence":"additional","affiliation":[{"name":"Department of Neurology Sean M. 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