{"artifact":{"id":"paper-fig-41569436-4","artifact_type":"paper_figure","entity_ids":"[]","title":"Fig. 4: Illustration of cytokine-mediated neuroinflammatory pathways linking gut–brain a...","quality_score":0.95,"created_by":"paper_figures_pipeline","provenance_chain":"[{\"source\": \"paper\", \"pmid\": \"41569436\", \"relation\": \"extracted_from\"}]","content_hash":"ceabe1f0c16f9d737c1543c7d7d6f2592be6b67a8b0b7f6492060bb9d3695610","metadata":{"doi":"","pmid":"41569436","pmcid":"PMC12891327","_origin":{"url":"https://www.ebi.ac.uk/europepmc/articles/PMC12891327/bin/10571_2026_1671_Fig4_HTML.jpg","type":"external","tracked_at":"2026-04-11T18:50:11.764093"},"caption":"Illustration of cytokine-mediated neuroinflammatory pathways linking gut–brain axis (GBA) dysfunction to Alzheimer’s disease (AD) pathology. Gut microbiota dysbiosis reduces short-chain fatty acids (SCFAs) and increases intestinal permeability, facilitating lipopolysaccharide (LPS) leakage into circulation and blood–brain barrier (BBB) disruption. Translocated LPS activates glial cells and promotes pro-inflammatory cytokine release (IL-1β, TNF-α, IL-6, IL-8, IFN-γ) through NF-κB, NLRP3, RAGE, and TRAIL signaling, leading to Aβ plaque deposition, tau hyperphosphorylation, and neuronal injury. In contrast, anti-inflammatory cytokines (IL-4, IL-10, TGF-β, IL-2, IL-3) modulate immune homeostasis via TREM2, PD-1/PD-L1, PI3K/Akt/mTOR, and cGAS–STING pathways. The imbalance between these signaling cascades drives chronic neuroinflammation and accelerates AD progression. Aβ amyloid-β, NF-κB nuclear factor kappa B, NLRP3 NOD-like receptor protein 3, RAGE receptor for advanced glycation end-prod","image_url":"https://www.ebi.ac.uk/europepmc/articles/PMC12891327/bin/10571_2026_1671_Fig4_HTML.jpg","image_path":"","description":"","figure_label":"Fig. 4","figure_number":4,"_schema_version":1,"source_strategy":"pmc_api","entities_mentioned":""},"created_at":"2026-04-11T11:50:11-07:00","updated_at":"2026-04-18T21:54:00.100607-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"external","origin_url":"https://www.ebi.ac.uk/europepmc/articles/PMC12891327/bin/10571_2026_1671_Fig4_HTML.jpg","lifecycle_changed_at":"2026-04-11T11:50:11-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":"ok","contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"f6c6d3e9-9cc4-4988-81a6-5bbecc9571aa","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"paper_figures_pipeline"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[{"target_artifact_id":"paper-41569436","link_type":"derives_from","strength":1.0,"evidence":"paper_figure metadata/provenance references PMID 41569436"}],"incoming_links":[],"current_artifact_id":"paper-fig-41569436-4","is_canonical":true,"supersede_chain":["paper-fig-41569436-4"]}