{"artifact":{"id":"hypothesis-h-92cfd75109","artifact_type":"hypothesis","entity_ids":"[]","title":"NRF2-Mediated Proteostatic Convergence: Shared Oxidative Stress Response Failure Links PD (SNCA Aggregation) and AD (Abeta/Tau Accumulation)","quality_score":0.7,"created_by":"hypothesis_page_handler","provenance_chain":"[]","content_hash":"2e0f826fe80034e12ade3abc38148b07b82871237f67ff1e0c09de5cc2fcf8c3","metadata":{"_origin":{"url":null,"type":"internal","tracked_at":"2026-04-28T15:09:39.751870"},"description":"Convergence hypothesis: NRF2 (NFE2L2) is the central transcriptional regulator whose failure explains parallel proteostatic collapse in both PD and AD, making it a high-priority cross-disease target.\n\nPD-specific mechanism: NRF2 regulates ARE-containing genes (HMOX1, NQO1, GCLC, GSTM1) that detoxify reactive oxygen species generated by mitochondrial dysfunction and neuromelanin iron accumulation. In PD, KEAP1 releases NRF2 in early disease to compensate, but chronic oxidative stress (elevated 4-","hypothesis_id":"h-92cfd75109","_schema_version":1},"created_at":"2026-04-28T08:09:39.751996-07:00","updated_at":"2026-04-28T08:09:39.751996-07:00","version_number":3,"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":"internal","origin_url":null,"lifecycle_changed_at":null,"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":"34e45ffa-1741-4c81-a938-cb74012e841f","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":"hypothesis_page_handler"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[{"source_artifact_id":"bench_ad_protein_aggregation_propensity_v1","link_type":"related","strength":0.75,"evidence":"AD Protein Aggregation Propensity benchmark seeded to evaluate hypotheses/gaps related to hypothesis-h-92cfd75109 (forge:benchmark_seed_2026-04-28)."}],"current_artifact_id":"hypothesis-h-92cfd75109","is_canonical":true,"supersede_chain":["hypothesis-h-92cfd75109"]}