{"id":"25f96fad-1dc9-5b4c-8061-0a1f20a5c69b","stable_key":"cea4b417-bb71-5d5d-8fe1-4e175aca750c:graviola-r406w-synergy","predicate":"interacts_with","statement":"Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"acdd5f80-c897-5ab2-82d8-7a74b4b48770","mechanism_event_label":"Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.","subject":{"id":"46b657b6-1692-59cb-bccd-e94db35a2734","slug":"annonacin","display_name":"Annonacin","entity_type_key":"small_molecule"},"object":{"id":"f7dd9991-bf06-59a8-8e76-92518a2a7afc","slug":"human-mapt-r406w","display_name":"Human MAPT R406W tau variant","entity_type_key":"protein_state"},"evidence_count":1,"mechanism_event":{"id":"acdd5f80-c897-5ab2-82d8-7a74b4b48770","stable_key":"cea4b417-bb71-5d5d-8fe1-4e175aca750c:graviola-r406w-synergy-event","event_type":"observed_relationship","label":"Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.","description":"Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"46b657b6-1692-59cb-bccd-e94db35a2734","slug":"annonacin","display_name":"Annonacin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"f7dd9991-bf06-59a8-8e76-92518a2a7afc","slug":"human-mapt-r406w","display_name":"Human MAPT R406W tau variant","entity_type_key":"protein_state"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"52ed9b7b-ec44-53f5-a35c-0cca445159fe","slug":"cdk5-p25-p35-axis","display_name":"CDK5 p25/p35 tau-kinase axis","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"dose","value_text":"Experimental annonacin exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"Study interval specified in the primary article","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"literature_reviewed; model-specific source-derived curation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"R406W-MAPT transgenic and non-transgenic mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Gene-environment interaction in a transgenic model does not establish penetrance or dose-response in humans.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Graviola (Annona muricata) chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings.","comparator":null,"unit":null,"notes":"","entity":{"slug":"graviola","display_name":"Graviola / Annona muricata","entity_type_key":"botanical"}},{"dimension":"organism","value_text":"R406W-MAPT transgenic and non-transgenic mice","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Annonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Annonacin, a natural lipophilic mitochondrial complex I inhibitor, increases phosphorylation of tau in the brain of FTDP-17 transgenic mice. (2014). https://pubmed.ncbi.nlm.nih.gov/24389273/ DOI: 10.1016/j.expneurol.2013.12.017","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"In vivo mouse exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Tau abundance, phosphorylation, localization and proteasomal activity","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"8df4d694-10ec-5190-8d27-cb1a50424582","evidence_kind":"source_excerpt","locator":"Lines 66-75","start_line":66,"end_line":75,"excerpt":"## graviola-r406w-synergy\nAnnonacin exposure produced greater tau accumulation, phosphorylation and redistribution in R406W-MAPT transgenic mice than in mice with endogenous mouse tau.\nModel/species: R406W-MAPT transgenic and non-transgenic mice\nTissue/system: Tau abundance, phosphorylation, localization and proteasomal activity\nExposure: Experimental annonacin exposure\nRoute: In vivo mouse exposure\nDuration: Study interval specified in the primary article\nLimits: Gene-environment interaction in a transgenic model does not establish penetrance or dose-response in humans.\nPrimary reference: Annonacin, a natural lipophilic mitochondrial complex I inhibitor, increases phosphorylation of tau in the brain of FTDP-17 transgenic mice. (2014). https://pubmed.ncbi.nlm.nih.gov/24389273/ DOI: 10.1016/j.expneurol.2013.12.017\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"R406W-MAPT transgenic and non-transgenic mice","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact original curation span with primary citation; not a publisher quotation.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dde73deb-4328-5cc7-aa41-04b7d845f4fa","stable_key":"import-cea4b417-bb71-5d5d-8fe1-4e175aca750c","title":"Graviola (Annona muricata): mechanism of action and interactions (2026-09-20)","document_type":"imported_text","citation_label":"Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. 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