{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T17:11:27Z","timestamp":1789146687989,"version":"build-2803163510"},"reference-count":50,"publisher":"National Academy of Sciences","issue":"37","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["NS087632"],"award-info":[{"award-number":["NS087632"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"DHAC | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1196590 and 2042089 and 2025931"],"award-info":[{"award-number":["1196590 and 2042089 and 2025931"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["Insititutional"],"award-info":[{"award-number":["Insititutional"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"\u5317\u4eac\u5e02\u79d1\u5b66\u6280\u672f\u59d4\u5458\u4f1a | Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["Institutional"],"award-info":[{"award-number":["Institutional"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470755 to Y.J.Z.; 32471252"],"award-info":[{"award-number":["32470755 to Y.J.Z.; 32471252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    Sterile alpha and Toll\/interleukin-1 receptor motif\u2013containing protein 1 (SARM1) is a NAD\n                    <jats:sup>+<\/jats:sup>\n                    -consuming enzyme that drives axon degeneration and is activated by changes in the NMN\/NAD\n                    <jats:sup>+<\/jats:sup>\n                    ratio. A recent study proposed that cytosolic double-stranded DNA (dsDNA) directly binds SARM1\u2019s TIR domain, activating it independently of this canonical mechanism. Here, we evaluate dsDNA-dependent SARM1 activation using purified SARM1, biochemical and biophysical assays, primary neurons, and cellular pharmacology. Across multiple platforms, dsDNA does not stimulate SARM1 NADase activity, promote higher-order assembly, or generate the metabolic signature of activated SARM1. When effects are observed, they are weak, context-dependent, and inconsistent across assays, and do not support a defined activation mechanism. In cells, dsDNA induces NAD\n                    <jats:sup>+<\/jats:sup>\n                    depletion through PARP-dependent pathways independently of SARM1. The reported DNA-binding mutant (3KE-SARM1) is nonfunctional in canonical SARM1 activation paradigms such as axotomy and therefore cannot be used to infer dsDNA activation mechanisms. Together, these findings do not support a model in which SARM1 is directly activated by dsDNA.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2620112123","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:43:57Z","timestamp":1789145037000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Direct activation of SARM1 by dsDNA is not supported by biochemical and cellular evidence"],"prefix":"10.1073","volume":"123","author":[{"given":"Allison H.","family":"Kao","sequence":"first","affiliation":[{"name":"Department of Developmental Biology, Washington University School of Medicine","place":["St. Louis"]},{"name":"Department of Genetics, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-3138","authenticated-orcid":false,"given":"Biswa P.","family":"Mishra","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biomedicine and Glycomics, Griffith University","place":["Gold Coast, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Sorbello","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/018kjjj71","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinyi","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wksha49","id-type":"ROR","asserted-by":"publisher"}],"name":"National Institute of Biological Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefeng","family":"Jiang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05kje8j93","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Pharmaceutical Sciences, Peking University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Masic","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biomedicine and Glycomics, Griffith University","place":["Gold Coast, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige","family":"Harten","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02sc3r913","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biomedicine and Glycomics, Griffith University","place":["Gold Coast, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixi","family":"Gu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/018kjjj71","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Centre, University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian Yuan","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02d5ks197","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Biomedical Health Sciences, School of Medicine, The Chinese University of Hong Kong","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Joseph","family":"Bloom","sequence":"additional","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine","place":["St. Louis"]},{"name":"Needleman Center for Neurometabolism and Axonal Therapeutics","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2680-4264","authenticated-orcid":false,"given":"Robi D.","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Genetics, Washington University School of Medicine","place":["St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4932-4343","authenticated-orcid":false,"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05kje8j93","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, Center for Life Sciences, Academy 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Kao Dataset for \u2018Direct activation of SARM1 by dsDNA is not supported by biochemical and cellular evidence.\u2019 Digital Commons Data@Becker. https:\/\/doi.org\/10.17632\/js8prhg99r. Deposited 9 September 2026."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2620112123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:44:00Z","timestamp":1789145040000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2620112123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":50,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2026,9,15]]}},"alternative-id":["10.1073\/pnas.2620112123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2620112123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"assertion":[{"value":"2026-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2620112123"}}