{"artifact":{"id":"paper-fig-16bf5354-7a8f-41fa-9507-574ca5efd6fa-4","artifact_type":"paper_figure","entity_ids":"[]","title":"FIGURE 4 — Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenera","quality_score":0.5,"created_by":"paper_figures_tool","provenance_chain":"[{\"step\": \"paper_figures_backfill\", \"pmid\": \"16bf5354-7a8f-41fa-9507-574ca5efd6fa\", \"timestamp\": \"2026-04-22T01:29:41.029618\"}]","content_hash":null,"metadata":{"pmid":"16bf5354-7a8f-41fa-9507-574ca5efd6fa","caption":"Connexins (Cxs)-mediated neuroglia crosstalk in multiple sclerosis. In multiple sclerosis (MS) the blood-brain barrier (BBB) becomes compromised, allowing B cells, T cells and monocytes to infiltrate the central nervous system (CNS) (1). Once crossed the BBB, activated macrophages secrete pro-inflammatory molecules that exacerbate neuronal suffering (2). The infiltrating immune cells trigger the activation of microglia (3) that, in turn, stimulate astrocytes toward a pro-inflammatory phenotype, establishing a self-perpetuating cycle of inflammation (4). Cx43-mediated crosstalk between astrocytes and microglia further elicited these processes. Specifically, Cx43 opening leads to ATP release that, acting on P2X7R on microglia, activates the NLRP3 inflammasome complex, leading to the cleavage of pro-caspase-1 into active caspase-1, which then process pro-Il-1β into its mature forms, released in the cytosol (4a). Conditional knockout (cKO) on astrocytes or blockade of Cx43 HCs leads to a r","image_url":"https://www.ebi.ac.uk/europepmc/articles/PMC11850338/bin/fncel-19-1532960-g004.jpg","paper_title":"Mechanistic insights into connexin-mediated neuroglia crosstalk in neurodegenerative diseases.","figure_label":"FIGURE 4","figure_number":4,"_schema_version":1,"source_strategy":"pmc_api"},"created_at":"2026-04-21T18:29:40.747630-07:00","updated_at":"2026-04-21T18:29:40.747630-07:00","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":null,"lifecycle_changed_at":"2026-04-21T18:29:40.747630-07:00","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":null,"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":"eaef9d8b-86af-4d9c-acc0-fa6ec30932b7","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_tool"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[],"current_artifact_id":"paper-fig-16bf5354-7a8f-41fa-9507-574ca5efd6fa-4","is_canonical":true,"supersede_chain":["paper-fig-16bf5354-7a8f-41fa-9507-574ca5efd6fa-4"]}