{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:56:27Z","timestamp":1785779787707,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,30]]},"group-title":"Neuroscience","reference-count":63,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["Merit Review I01-RX005045"],"award-info":[{"award-number":["Merit Review I01-RX005045"]}],"id":[{"id":"https:\/\/ror.org\/05rsv9s98","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Center Grant I50-RX004845"],"award-info":[{"award-number":["Center Grant I50-RX004845"]}],"id":[{"id":"https:\/\/ror.org\/05rsv9s98","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NIAMS R01-AR083489"],"award-info":[{"award-number":["NIAMS R01-AR083489"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["NINDS R01-NS128086"],"award-info":[{"award-number":["NINDS R01-NS128086"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Wallerian degeneration of anucleated axonal segments is driven by SARM1, which depletes axonal NAD+, disrupting energy metabolism and triggering self-destruction. SARM1 inhibition is an emerging therapeutic target for traumatic nerve injuries. Boldine, a natural aporphine alkaloid from\n                  <jats:italic>Peumus boldus<\/jats:italic>\n                  , modulates connexin hemichannels, oxidative stress, and inflammation. Building on our published work showing boldine\u2019s neuroprotective effects in nerve injury models, we hypothesized that boldine also inhibits SARM1 directly. A fluorescence polarization assay revealed that boldine inhibits SARM1 NADase activity with an IC50 of approximately 7.5 uM. AI-assisted structural modeling (AlphaFold3-based Boltz-1 with GNINA docking) predicted two boldine binding sites on SARM1: the TIR catalytic site (Kd \u223c 13.5 uM) and the ARM-TIR regulatory interface (Kd \u223c 12 uM). In a sciatic nerve explant model, boldine preserved the integrity of anucleated axonal segments at 3 and 7 days post-transection relative to vehicle controls. These findings suggest boldine may act as a dual-site SARM1 inhibitor and support its development as a neuroprotective therapy after traumatic axonal injury.\n                <\/jats:p>","DOI":"10.64898\/2026.07.27.741059","type":"posted-content","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:10:20Z","timestamp":1785435020000},"source":"Crossref","is-referenced-by-count":0,"title":["Boldine inhibits SARM1 NADase Activity and Preserves Axonal Integrity After Nerve Injury"],"prefix":"10.64898","author":[{"given":"Justin C.","family":"Burrell","sequence":"first","affiliation":[{"name":"Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA"},{"name":"Center for Innovation & Precision Dentistry, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Oral & Maxillofacial Surgery, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomisin T.","family":"Latona","sequence":"additional","affiliation":[{"name":"Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Clizbe","sequence":"additional","affiliation":[{"name":"Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykhailo M.","family":"Tatarchuk","sequence":"additional","affiliation":[{"name":"Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Toro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Spinal Cord Damage Research Center, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexa N.","family":"Olivarez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong V.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy Z.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Texas at Austin, Austin, TX, USA"},{"name":"Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Cardozo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Spinal Cord Damage Research Center, James J. 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