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Ferroptosis Validation in Parkinson's Disease
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experiment
Created: 2026-04-02T10:01:41
By: crosslink-v2
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ID: experiment-exp-wiki-experiments-ferropto
🧫 Experiment Protocol
Clinicalproposed
SUMMARY
# Ferroptosis Validation in Parkinson's Disease
## Background and Rationale
This clinical validation study investigates ferroptosis as a therapeutic target in Parkinson's disease (PD), building on emerging evidence that iron-dependent lipid peroxidation contributes significantly to dopaminergic neurodegeneration. Ferroptosis, a distinct form of regulated cell death characterized by iron accumulation and lipid peroxidation, has been implicated in PD pathogenesis through multiple mechanisms includ
METHODOLOGY NOTES
**Phase 1: In Vitro Model Development (Months 1-12)**
• Establish primary dopaminergic neuronal cultures from human iPSCs differentiated using FOXA2/LMX1A protocol
• Generate isogenic PD patient-derived iPSC lines with SNCA, LRRK2, and PRKN mutations (n=30 lines per mutation)
• Develop ferroptosis induction protocols using erastin (10-20 μM), RSL3 (1-5 μM), and FIN56 (2-10 μM)
• Validate ferroptosis markers: lipid peroxidation (C11-BODIPY), iron accumulation (calcein-AM quenching), GPX4 depletion
• Screen ferroptosis inhibitors: ferrostatin-1 (1-10 μM), liproxstatin-1 (1-5 μM), vitamin E (50-200 μM)
• Measure ATP production, mitochondrial membrane potential, and ROS levels using fluorometric assays
**Phase 2: Biomarker Validation (Months 13-24)**
• Recruit early-stage PD patients (n=150, Hoehn-Yahr Stage 1-2, UPDRS-III 10-40)
• Recruit age-matched healthy controls (n=75)
• Collect cerebrospinal fluid via lumbar puncture and plasma samples
• Quantify ferroptosis biomarkers: 4-hydroxy
▸Metadatasource: {'type': 'manual', 'source_name': 'wiki'
| source | {'type': 'manual', 'source_name': 'wiki', 'extracted_by': 'backfill_v1', 'extraction_date': '2026-04-16T01:00:16.906934Z'} |
| summary | # Ferroptosis Validation in Parkinson's Disease ## Background and Rationale This clinical validation study investigates ferroptosis as a therapeutic target in Parkinson's disease (PD), building on eme |
| entities | {'genes': ['FERRO'], 'diseases': ["Parkinson's Disease"]} |
| model_system | human |
| _schema_version | 1 |
| experiment_type | clinical |
| primary_outcome | Demonstration of neuroprotective efficacy of ferroptosis inhibitors in preventing dopaminergic neuron loss in α-synuclein transgenic mouse models and patient-derived cellular systems. |
| methodology_notes | **Phase 1: In Vitro Model Development (Months 1-12)** • Establish primary dopaminergic neuronal cultures from human iPSCs differentiated using FOXA2/LMX1A protocol • Generate isogenic PD patient-deri |
| replication_status | single_study |
| extraction_metadata | {'backfill_at': '2026-04-16T01:00:16.906942', 'needs_review': True, 'extraction_notes': 'Backfilled from wiki source (no PMID available)', 'extraction_confidence': 0.4} |
📊 Evidence Profile
Foundational
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Certainty
100%
Debates
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Incoming
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Outgoing
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derives from (16)
experiment-exp-wiki-experiment→hypothesis-h-7957bb2ahypothesis-h-7957bb2a→analysis-SDA-2026-04-01-gap-01analysis-SDA-2026-04-01-gap-01→hypothesis-h-7957bb2aexperiment-exp-wiki-experiment→hypothesis-h-aa8b4952hypothesis-h-aa8b4952→analysis-SDA-2026-04-01-gap-00
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analysis-SDA-2026-04-01-gap-00→hypothesis-h-aa8b4952experiment-exp-wiki-experiment→hypothesis-h-fd1562a3hypothesis-h-fd1562a3→analysis-SDA-2026-04-01-gap-v2analysis-SDA-2026-04-01-gap-v2→hypothesis-h-fd1562a3analysis-SDA-2026-04-01-gap-v2→hypothesis-h-98b431baexperiment-exp-wiki-experiment→hypothesis-h-98b431bahypothesis-h-98b431ba→analysis-SDA-2026-04-01-gap-v2experiment-exp-wiki-experiment→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→analysis-SDA-2026-04-01-gap-00analysis-SDA-2026-04-01-gap-00→hypothesis-h-969bd8e0experiment-exp-wiki-experiment→wiki-experiments-ferroptosis-p
supports (31)
hypothesis-h-969bd8e0→paper-38877020paper-38877020→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-34873283paper-34873283→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-24431222
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paper-24431222→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-39913247paper-39913247→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-40598228paper-40598228→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-41678910paper-41678910→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-41914243paper-41914243→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-32710675paper-32710675→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-31564441paper-31564441→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-41692009paper-41692009→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-41900832paper-41900832→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-41227383paper-41227383→hypothesis-h-969bd8e0hypothesis-h-969bd8e0→paper-41817167paper-41817167→hypothesis-h-969bd8e0experiment-exp-wiki-experiment→hypothesis-h-7957bb2aexperiment-exp-wiki-experiment→hypothesis-h-aa8b4952experiment-exp-wiki-experiment→hypothesis-h-fd1562a3experiment-exp-wiki-experiment→hypothesis-h-98b431baexperiment-exp-wiki-experiment→hypothesis-h-969bd8e0
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