{"id":"86f3bf3c-95e8-54e3-a6a1-478fb1d99295","stable_key":"b7798a90-72a3-5454-a321-c4be88bf0cc4:lithium-gsk3-rescue","predicate":"rescues","statement":"GSK3 inhibition restored amyloid uptake/degradation in microglia from lithium-depleted mice.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ce0a8ada-9658-5bac-81ce-6c2d62971dc1","mechanism_event_label":"Blocking the downstream enzyme helped test the proposed chain.","subject":{"id":"23d845a1-80c5-5f36-b262-5718344fcf4e","slug":"chir99021","display_name":"CHIR99021","entity_type_key":"small_molecule"},"object":{"id":"01c70886-9b77-5452-bcdf-88fa437fd0ea","slug":"mouse-microglial-amyloid-clearance","display_name":"Mouse microglial amyloid uptake and degradation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ce0a8ada-9658-5bac-81ce-6c2d62971dc1","stable_key":"b7798a90-72a3-5454-a321-c4be88bf0cc4:lithium-gsk3-rescue-event","event_type":"observed_relationship","label":"Blocking the downstream enzyme helped test the proposed chain.","description":"GSK3 inhibition restored amyloid uptake/degradation in microglia from lithium-depleted mice.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"23d845a1-80c5-5f36-b262-5718344fcf4e","slug":"chir99021","display_name":"CHIR99021","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"01c70886-9b77-5452-bcdf-88fa437fd0ea","slug":"mouse-microglial-amyloid-clearance","display_name":"Mouse microglial amyloid uptake and degradation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"8e2e3902-5e26-52e3-9c85-1d7c0ace1637","slug":"lithium","display_name":"Lithium","entity_type_key":"nutrient_element"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"13b4b09c-4581-58f6-9792-9a78125963e8","slug":"lithium-ion","display_name":"Lithium ion (Li+)","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"e7b85cc5-eead-5551-ba6d-40420edd8156","slug":"mouse-gsk3b","display_name":"Mouse glycogen synthase kinase 3 beta / Gsk3b","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"fb76d6c2-e8a0-5c22-8ebb-f06e4c66d50c","slug":"mouse-cortical-lithium-availability","display_name":"Mouse cortical lithium availability","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"CHIR99021 and companion PF-04802367 rescue assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Inhibitor rescue supports partial mediation, not a single-target explanation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lithium","display_name":"Lithium","entity_type_key":"nutrient_element"}},{"dimension":"plain_language","value_text":"Blocking the downstream enzyme helped test the proposed chain.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Lithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"d52a3de7-eaf5-5efe-9266-50b5da3e4206","evidence_kind":"source_excerpt","locator":"Lines 488-494","start_line":488,"end_line":494,"excerpt":"## lithium-gsk3-rescue\nBlocking the downstream enzyme helped test the proposed chain.\nGSK3 inhibition restored amyloid uptake/degradation in microglia from lithium-depleted mice.\nModel: CHIR99021 and companion PF-04802367 rescue assays.\nLimitations: Inhibitor rescue supports partial mediation, not a single-target explanation.\nEvidence access: Primary full text\nLithium deficiency and the onset of Alzheimer's disease. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40770094/ · DOI 10.1038/s41586-025-09335-x","model_system":"CHIR99021 and companion PF-04802367 rescue assays.","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":"b2dd2f3c-5c4c-5a12-9a0d-91b521ffcf98","stable_key":"import-b7798a90-72a3-5454-a321-c4be88bf0cc4","title":"Lithium: metal-sensitive enzymes, transport 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":"dc67e965ba78458cf2d88d000d687641d9104354115ab16529a3a64941bd777d","revision_id":"4af127bf-9ccc-516b-9481-fafd453c2c35","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}