{"artifact":{"id":"experiment-exp-wiki-experiments-alpha-synuclein-spreading-neurodegeneration-pd","artifact_type":"experiment","entity_ids":null,"title":"Alpha-Synuclein Spreading Mechanism — Prion-Like Propagation and Neurodegeneration","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.904198Z"},"summary":"# Alpha-Synuclein Spreading Mechanism — Prion-Like Propagation and Neurodegeneration\n## Background and Rationale\nAlpha-synuclein spreading through prion-like propagation mechanisms represents one of the most significant paradigm shifts in our understanding of Parkinson's disease pathogenesis and offers unprecedented opportunities for therapeutic intervention. This neuronal protein, encoded by the SNCA gene located on chromosome 4q22.1, normally functions as a synaptic protein involved in vesicle","entities":{"genes":["ADRA2A/DNMT1/HSPA1A"],"diseases":["Parkinson's Disease"]},"model_system":"human","_schema_version":1,"experiment_type":"exploratory","primary_outcome":"Validate Alpha-Synuclein Spreading Mechanism — Prion-Like Propagation and Neurodegeneration","methodology_notes":"**Phase 1: Human Brain Tissue Collection and Processing (Weeks 1-4)**\n• Obtain postmortem brain tissue from 30 confirmed PD patients and 15 age-matched controls through established brain banks\n• Collect samples from substantia nigra, striatum, cortex, and brainstem regions within 12 hours of death\n• Process tissues for histological analysis, protein extraction, and cryo-preservation at -80°C\n• Perform immunohistochemical staining using anti-α-synuclein antibodies (Syn211, LB509) to confirm pathological aggregates\n\n**Phase 2: Alpha-Synuclein Aggregate Isolation and Characterization (Weeks 5-8)**\n• Extract pathological α-synuclein aggregates from PD brain tissue using sarkosyl-insoluble fractionation protocol\n• Characterize aggregate morphology using transmission electron microscopy and atomic force microscopy\n• Analyze aggregate composition using mass spectrometry and Western blot with conformation-specific antibodies\n• Quantify seeding activity using real-time quaking-induced conversio","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.904206","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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LRRK2"},{"source_artifact_id":"wiki-entities-lrrk2","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-institutions-lrrk2-consortium","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-cell-types-brain-derived-neurotrophic-factor-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BDNF"},{"source_artifact_id":"wiki-proteins-lrrk2","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-proteins-lamp2a","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LAMP2A"},{"source_artifact_id":"wiki-diseases-snca-variants","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNCA"},{"source_artifact_id":"wiki-mechanisms-lrrk2-pathway-parkinson-disease","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-entities-prasinezumab","link_type":"mentions","strength":0.6,"evidence":"Title match: prasinezumab"},{"source_artifact_id":"wiki-diseases-msa","link_type":"mentions","strength":0.6,"evidence":"Title match: Multiple System Atrophy"},{"source_artifact_id":"wiki-investment-bdnf-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BDNF"},{"source_artifact_id":"wiki-experiments-lrrk2-gba-carrier-resilience-pd","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-ideas-lrrk2-inhibitor-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-genes-snca","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNCA"},{"source_artifact_id":"wiki-therapeutics-lrrk2-inhibitors","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-diseases-lrrk2-variants","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-mechanisms-autophagy","link_type":"mentions","strength":0.6,"evidence":"Title match: autophagy"},{"source_artifact_id":"wiki-proteins-ck2-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: CK2"},{"source_artifact_id":"wiki-entities-lrrk2-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-proteins-snap25-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNAP"},{"source_artifact_id":"wiki-models-lrrk2-g2019s-transgenic-mouse-model","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-proteins-snare-complex","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNARE"},{"source_artifact_id":"wiki-proteins-bdnf-protein","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BDNF"},{"source_artifact_id":"wiki-mechanisms-lrrk2-kinase-pathway-parkinsons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-mechanisms-lrrk2-14-3-3-interaction-network","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-therapeutics-lrrk2-inhibitor-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-therapeutics-bdnf-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BDNF"},{"source_artifact_id":"wiki-mechanisms-lrrk2-cbs-tauopathies","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-proteins-bdnf","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BDNF"},{"source_artifact_id":"wiki-events","link_type":"mentions","strength":0.6,"evidence":"Title match: 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LRRK2"},{"source_artifact_id":"wiki-diseases-prion-diseases","link_type":"mentions","strength":0.6,"evidence":"Title match: Prion Diseases"},{"source_artifact_id":"wiki-biomarkers-snap25","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNAP"},{"source_artifact_id":"wiki-cell-types-bdnf-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: BDNF"},{"source_artifact_id":"wiki-mechanisms-prion-like-propagation-hypothesis","link_type":"mentions","strength":0.6,"evidence":"Title match: Prion-Like Propagation Hypothesis"},{"source_artifact_id":"wiki-entities-autophagy","link_type":"mentions","strength":0.6,"evidence":"Title match: Autophagy"},{"source_artifact_id":"wiki-mechanisms-lrrk2-transgenic-mouse","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-mechanisms-pd-lrrk2-pathway","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-cell-types-dopaminergic-neurons","link_type":"mentions","strength":0.6,"evidence":"Title match: Dopaminergic Neurons"},{"source_artifact_id":"wiki-diseases-multiple-system-atrophy","link_type":"mentions","strength":0.6,"evidence":"Title match: Multiple System Atrophy"},{"source_artifact_id":"wiki-therapeutics-lrrk2-gba-combination-therapy","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-brain-regions","link_type":"mentions","strength":0.6,"evidence":"Title match: Brain Regions"},{"source_artifact_id":"wiki-mechanisms-lrrk2-pathway-parkinsons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-cell-types-lrrk2-g2019s-dopaminergic-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-cell-types-lrrk2-dopamine-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-diseases-lrrk2-g2019s","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-mechanisms-lrrk2-pathway","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-therapeutics-lrrk2-kinase-targeting-therapies","link_type":"mentions","strength":0.7,"evidence":"Gene mention: LRRK2"},{"source_artifact_id":"wiki-gaps","link_type":"mentions","strength":0.6,"evidence":"Title match: Knowledge Gaps"},{"source_artifact_id":"wiki-proteins-parkin","link_type":"mentions","strength":0.6,"evidence":"Title match: Parkin"},{"source_artifact_id":"wiki-cell-types-snca-overexpressing-dopaminergic-neurons","link_type":"mentions","strength":0.7,"evidence":"Gene mention: SNCA"},{"source_artifact_id":"wiki-experiments-alpha-synuclein-spreading-neurodegeneration-pd","link_type":"mentions","strength":0.6,"evidence":"Title match: Alpha-Synuclein Spreading Mechanism — Prion-Like Propagation 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LRRK2"},{"source_artifact_id":"wiki-genes-plk2","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PLK2"},{"source_artifact_id":"wiki-proteins-hepsin","link_type":"mentions","strength":0.6,"evidence":"Wiki page 'Hepsin Protein' mentions entity found in experiment"},{"source_artifact_id":"wiki-proteins-prkn-protein","link_type":"mentions","strength":0.6,"evidence":"Wiki page 'Parkin Protein' mentions entity found in experiment"},{"source_artifact_id":"wiki-genes-adra2a","link_type":"mentions","strength":0.7,"evidence":"Gene match: ADRA2A"},{"source_artifact_id":"wiki-genes-dnmt1","link_type":"mentions","strength":0.7,"evidence":"Gene match: DNMT1"},{"source_artifact_id":"wiki-genes-hspa1a","link_type":"mentions","strength":0.7,"evidence":"Gene match: HSPA1A"},{"source_artifact_id":"wiki-proteins","link_type":"mentions","strength":0.5,"evidence":"Content: HSPA1A mentioned 3x in 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