{"id":"8071e418-3495-59ec-a177-780e943f451b","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-sarm-ratio","predicate":"activates","statement":"Increasing NMN relative to NAD+ increased NADase activity of purified human SARM1 residues 28–724, which retain ARM, SAM and TIR domains but lack the mitochondrial targeting sequence.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"cf0a6d5a-c606-5a5e-9f53-e6ee237a28c6","mechanism_event_label":"The balance between a precursor and finished NAD can activate a destructive feedback loop.","subject":{"id":"d1c59139-db61-5fa0-a25d-40c3e625152e","slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"},"object":{"id":"7720c9fc-9084-5beb-b9e3-b83a71055e30","slug":"human-sarm1-28-724","display_name":"Human SARM1 residues 28–724","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cf0a6d5a-c606-5a5e-9f53-e6ee237a28c6","stable_key":"8c946991-97f0-55ee-8df0-00e67621962f:nad-plus-sarm-ratio-event","event_type":"observed_relationship","label":"The balance between a precursor and finished NAD can activate a destructive feedback loop.","description":"Increasing NMN relative to NAD+ increased NADase activity of purified human SARM1 residues 28–724, which retain ARM, SAM and TIR domains but lack the mitochondrial targeting sequence.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d1c59139-db61-5fa0-a25d-40c3e625152e","slug":"nmn","display_name":"NMN","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"7720c9fc-9084-5beb-b9e3-b83a71055e30","slug":"human-sarm1-28-724","display_name":"Human SARM1 residues 28–724","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human construct; NMR activity assays and cell experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"NAD+ is also the catalytic substrate, so activity cannot be inferred from ratio alone across all conditions. This does not show oral NMN causes nerve injury.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"The balance between a precursor and finished NAD can activate a destructive feedback loop.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"bef1be85-a940-582b-b058-983a9200f03b","evidence_kind":"source_excerpt","locator":"Lines 76-82","start_line":76,"end_line":82,"excerpt":"## nad-plus-sarm-ratio\nThe balance between a precursor and finished NAD can activate a destructive feedback loop.\nIncreasing NMN relative to NAD+ increased NADase activity of purified human SARM1 residues 28–724, which retain ARM, SAM and TIR domains but lack the mitochondrial targeting sequence.\nModel: Purified human construct; NMR activity assays and cell experiments.\nLimitations: NAD+ is also the catalytic substrate, so activity cannot be inferred from ratio alone across all conditions. This does not show oral NMN causes nerve injury.\nEvidence access: Primary full text\nSARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33657413/ · DOI 10.1016/j.neuron.2021.02.009","model_system":"Purified human construct; NMR activity assays and cell experiments.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"f59aa302-d463-5462-876f-e21e64861eac","stable_key":"import-8c946991-97f0-55ee-8df0-00e67621962f","title":"NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"9f5324d0d652c80ad630b3100e28ce34cd2ce260ea2e1324332a4262ce72ae09","revision_id":"0e07909c-e8bc-5950-bafc-61371d9d6412","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}