{"artifact":{"id":"experiment-exp-wiki-experiments-epigenetic-regulation-neurodegeneration","artifact_type":"experiment","entity_ids":null,"title":"Epigenetic Regulation Dysfunction in Alzheimer's and Parkinson's Disease","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":"2026-04-16T01:00:16.901261Z"},"summary":"# Epigenetic Regulation Dysfunction in Alzheimer's and Parkinson's Disease\n## Background and Rationale\nNeurodegenerative diseases like Alzheimer's (AD) and Parkinson's disease (PD) exhibit complex pathophysiology involving genetic, environmental, and epigenetic factors. Growing evidence suggests that epigenetic dysregulation plays a crucial role in disease onset and progression, affecting gene expression patterns critical for neuronal survival and function. This comprehensive clinical study aims","entities":{"genes":["BRD4/HDAC/HDAC3"],"diseases":["Alzheimer's Disease"]},"model_system":"human","_schema_version":1,"experiment_type":"clinical","primary_outcome":"Validate Epigenetic Regulation Dysfunction in Alzheimer's and Parkinson's Disease","methodology_notes":"Phase 1: Sample Collection and Processing (Months 1-6): Collect post-mortem brain tissue from frontal cortex, hippocampus, and substantia nigra regions from AD (n=60), PD (n=60), and control (n=40) subjects. Establish iPSC lines from patient fibroblasts using Sendai virus reprogramming. Phase 2: iPSC Differentiation (Months 4-12): Differentiate iPSCs into dopaminergic neurons using dual-SMAD inhibition protocol with SB431542 and LDN193189, followed by FGF8 and SHH treatment. Generate cholinergic neurons using NGF and BDNF supplementation. Validate neuronal identity using immunofluorescence for TH, ChAT, and MAP2. Phase 3: Epigenetic Profiling (Months 7-18): Extract high-quality DNA and RNA using AllPrep DNA/RNA Mini Kit. Perform RRBS library preparation using MspI digestion and bisulfite conversion. Conduct ChIP-seq using antibodies against H3K4me3, H3K27me3, and H3K9ac with 10μg chromatin per immunoprecipitation. Generate RNA-seq libraries including small RNA fractions using TruSeq pr","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.901267","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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wiki/mechanisms-htt-huntingtin-hd-causal-chain"},{"source_artifact_id":"wiki-mechanisms-htt-transcriptional-dysregulation-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 4x in wiki/mechanisms-htt-transcriptional-dysregulation-pathway"},{"source_artifact_id":"wiki-mechanisms-transcription-regulation-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 4x in wiki/mechanisms-transcription-regulation-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-als-neuroinflammation","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-als-neuroinflammation"},{"source_artifact_id":"wiki-mechanisms-ad-combination-therapy-matrix","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/mechanisms-ad-combination-therapy-matrix"},{"source_artifact_id":"wiki-mechanisms-histone-modification-pathway-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 20x in wiki/mechanisms-histone-modification-pathway-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-parkinsons-neuroinflammation","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/mechanisms-parkinsons-neuroinflammation"},{"source_artifact_id":"wiki-mechanisms-acly-alpha-synuclein-autophagy","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-acly-alpha-synuclein-autophagy"},{"source_artifact_id":"wiki-mechanisms-als-combination-therapy-matrix","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/mechanisms-als-combination-therapy-matrix"},{"source_artifact_id":"wiki-mechanisms-pdlim7-epigenetic-activation-pd","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-pdlim7-epigenetic-activation-pd"},{"source_artifact_id":"wiki-mechanisms-epigenetic-changes-psp","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 4x in wiki/mechanisms-epigenetic-changes-psp"},{"source_artifact_id":"wiki-mechanisms-short-chain-fatty-acids","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 11x in wiki/mechanisms-short-chain-fatty-acids"},{"source_artifact_id":"wiki-mechanisms-creb-independent-neuronal-survival-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 4x in wiki/mechanisms-creb-independent-neuronal-survival-pathway"},{"source_artifact_id":"wiki-mechanisms-scfa-therapy-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 11x in wiki/mechanisms-scfa-therapy-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-abca1-cholesterol-efflux-apoe-lipidation-ad-causal-chain","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-abca1-cholesterol-efflux-apoe-lipidation-ad-causal-chain"},{"source_artifact_id":"wiki-mechanisms-creb-independent-neuronal-survival-pathways","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 6x in wiki/mechanisms-creb-independent-neuronal-survival-pathways"},{"source_artifact_id":"wiki-mechanisms-transcriptional-regulation","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 5x in wiki/mechanisms-transcriptional-regulation"},{"source_artifact_id":"wiki-mechanisms-protein-sumoylation-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/mechanisms-protein-sumoylation-pathway"},{"source_artifact_id":"wiki-mechanisms-psp-epigenetic-changes","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 9x in wiki/mechanisms-psp-epigenetic-changes"},{"source_artifact_id":"wiki-mechanisms-epigenetic-alterations-ad","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 24x in wiki/mechanisms-epigenetic-alterations-ad"},{"source_artifact_id":"wiki-mechanisms-msa-genetics-risk-factors","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-msa-genetics-risk-factors"},{"source_artifact_id":"wiki-mechanisms-nf-kappa-b-signaling-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 5x in wiki/mechanisms-nf-kappa-b-signaling-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-chromatin-remodeling-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 8x in wiki/mechanisms-chromatin-remodeling-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-metabolic-epigenetic-axis-neurodegeneration-synthesis","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-metabolic-epigenetic-axis-neurodegeneration-synthesis"},{"source_artifact_id":"wiki-mechanisms-adult-neurogenesis-neurodegeneration","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-adult-neurogenesis-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-chromatin-remodeling-epigenetic-therapy-neurodegeneration-synthesis","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 16x in wiki/mechanisms-chromatin-remodeling-epigenetic-therapy-neurodegeneration-synthesis"},{"source_artifact_id":"wiki-mechanisms-epigenetic-disease-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 13x in wiki/mechanisms-epigenetic-disease-comparison"},{"source_artifact_id":"wiki-mechanisms-epigenetic-dysregulation-4r-tauopathies","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 5x in wiki/mechanisms-epigenetic-dysregulation-4r-tauopathies"},{"source_artifact_id":"wiki-mechanisms-epigenetic-dysregulation-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 6x in wiki/mechanisms-epigenetic-dysregulation-pathway"},{"source_artifact_id":"wiki-mechanisms-neuroplasticity","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/mechanisms-neuroplasticity"},{"source_artifact_id":"wiki-mechanisms-transcription-regulation","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 5x in wiki/mechanisms-transcription-regulation"},{"source_artifact_id":"wiki-mechanisms-epigenetics-psp","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 6x in wiki/mechanisms-epigenetics-psp"},{"source_artifact_id":"wiki-mechanisms-selective-neuronal-vulnerability","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-selective-neuronal-vulnerability"},{"source_artifact_id":"wiki-mechanisms-picalm-clathrin-endocytosis-ad-causal-chain","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/mechanisms-picalm-clathrin-endocytosis-ad-causal-chain"},{"source_artifact_id":"wiki-mechanisms-synaptic-plasticity-deficits","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-synaptic-plasticity-deficits"},{"source_artifact_id":"wiki-mechanisms-disease-mechanism-taxonomy","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-disease-mechanism-taxonomy"},{"source_artifact_id":"wiki-mechanisms-trinucleotide-repeat-expansion","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-trinucleotide-repeat-expansion"},{"source_artifact_id":"wiki-mechanisms-lactate-lactylation-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 12x in wiki/mechanisms-lactate-lactylation-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-epigenetics-als","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 11x in wiki/mechanisms-epigenetics-als"},{"source_artifact_id":"wiki-mechanisms-chromatin-remodeling","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 27x in wiki/mechanisms-chromatin-remodeling"},{"source_artifact_id":"wiki-mechanisms-microbiome-gut-brain-axis-parkinsons","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-microbiome-gut-brain-axis-parkinsons"},{"source_artifact_id":"wiki-mechanisms-epigenetics-parkinsons","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 6x in wiki/mechanisms-epigenetics-parkinsons"},{"source_artifact_id":"wiki-mechanisms-mitochondrial-unfolded-protein-response","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-mitochondrial-unfolded-protein-response"},{"source_artifact_id":"wiki-mechanisms-small-molecule-derivatives-neurodegenerative-pathways","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-small-molecule-derivatives-neurodegenerative-pathways"},{"source_artifact_id":"wiki-mechanisms-epigenetic-dysregulation-comparison","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 26x in wiki/mechanisms-epigenetic-dysregulation-comparison"},{"source_artifact_id":"wiki-mechanisms-cbs-epigenetic-mechanisms","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 11x in wiki/mechanisms-cbs-epigenetic-mechanisms"},{"source_artifact_id":"wiki-mechanisms-epigenetic-dysregulation-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 7x in wiki/mechanisms-epigenetic-dysregulation-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-cd2ap-synaptic-dysfunction-ad-causal-chain","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 4x in wiki/mechanisms-cd2ap-synaptic-dysfunction-ad-causal-chain"},{"source_artifact_id":"wiki-mechanisms-hdac-inhibitor-mechanism","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 45x in wiki/mechanisms-hdac-inhibitor-mechanism"},{"source_artifact_id":"wiki-mechanisms-lncrna-signaling-neurodegeneration","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-lncrna-signaling-neurodegeneration"},{"source_artifact_id":"wiki-mechanisms-ad-epigenetic-alterations-pathway","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 19x in wiki/mechanisms-ad-epigenetic-alterations-pathway"},{"source_artifact_id":"wiki-mechanisms-neurogenesis-ad-superagers","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC mentioned 2x in wiki/mechanisms-neurogenesis-ad-superagers"},{"source_artifact_id":"wiki-biomarkers-epigenetic-biomarkers-neurodegeneration","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 4x in wiki/biomarkers-epigenetic-biomarkers-neurodegeneration"},{"source_artifact_id":"wiki-entities-hdac-enzymes","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 30x in wiki/entities-hdac-enzymes"},{"source_artifact_id":"wiki-entities-histone-deacetylase","link_type":"mentions","strength":0.44999999999999996,"evidence":"Content: HDAC3 mentioned 2x in wiki/entities-histone-deacetylase"},{"source_artifact_id":"wiki-experiments-epigenetic-dysregulation-hd","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 5x in wiki/experiments-epigenetic-dysregulation-hd"},{"source_artifact_id":"wiki-experiments-epigenetic-dysregulation-parkinsons","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/experiments-epigenetic-dysregulation-parkinsons"},{"source_artifact_id":"wiki-experiments-microglial-aging-immune-memory","link_type":"mentions","strength":0.5,"evidence":"Content: HDAC mentioned 3x in wiki/experiments-microglial-aging-immune-memory"},{"source_artifact_id":"hypothesis-h-0e675a41","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-wiki-experiments-epigenetic-regulation-neurodegeneration"},{"source_artifact_id":"hypothesis-h-addc0a61","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-wiki-experiments-epigenetic-regulation-neurodegeneration"},{"source_artifact_id":"hypothesis-h-8fe389e8","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-wiki-experiments-epigenetic-regulation-neurodegeneration"},{"source_artifact_id":"hypothesis-h-a90e2e89","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment exp-wiki-experiments-epigenetic-regulation-neurodegeneration"},{"source_artifact_id":"hypothesis-h-d7121bcc","link_type":"related","strength":0.85,"evidence":"Hypothesis tested by experiment 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experiment title"},{"source_artifact_id":"wiki-entities-parkin-protein","link_type":"mentions","strength":0.5,"evidence":"Entity 'PARKIN' in experiment title"},{"source_artifact_id":"wiki-circuits-alzheimer-hippocampal-circuit","link_type":"mentions","strength":0.5,"evidence":"Entity 'ALZHEIMER' in experiment title"},{"source_artifact_id":"wiki-institutions-alzheimer-europe","link_type":"mentions","strength":0.5,"evidence":"Entity 'ALZHEIMER' in experiment title"},{"source_artifact_id":"wiki-institutions-alzheimer-indonesia","link_type":"mentions","strength":0.5,"evidence":"Entity 'ALZHEIMER' in experiment title"},{"source_artifact_id":"wiki-circuits-parkinson-basal-ganglia-circuit","link_type":"mentions","strength":0.5,"evidence":"Entity 'PARKINSON' in experiment title"},{"source_artifact_id":"wiki-cell-types-spinal-interneurons-motor-neuron-disease","link_type":"mentions","strength":0.5,"evidence":"Entity 'DISEASE' in experiment 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Hypotheses"},{"source_artifact_id":"wiki-biomarkers-mri-atrophy-cbs-psp","link_type":"mentions","strength":0.7,"evidence":"Gene mention: MRI"},{"source_artifact_id":"wiki-technologies-magnetic-resonance-imaging","link_type":"mentions","strength":0.7,"evidence":"Gene mention: MRI"},{"source_artifact_id":"wiki-diagnostics-neuroimaging","link_type":"mentions","strength":0.6,"evidence":"Title match: neuroimaging"},{"source_artifact_id":"wiki-events-aaic-2026-biomarker-integration-pet-fluid-combination","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PET"},{"source_artifact_id":"wiki-technologies-pet-imaging","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PET"},{"source_artifact_id":"wiki-experiments","link_type":"mentions","strength":0.6,"evidence":"Title match: Experiments"},{"source_artifact_id":"wiki-diagnostics-mri-findings-in-corticobasal-syndrome","link_type":"mentions","strength":0.7,"evidence":"Gene mention: MRI"},{"source_artifact_id":"wiki-diagnostics-pet-imaging","link_type":"mentions","strength":0.7,"evidence":"Gene mention: PET"},{"source_artifact_id":"wiki-projects-adni","link_type":"related","strength":0.6,"evidence":"Wiki disease page related to experiment about Alzheimer's Disease"},{"source_artifact_id":"wiki-genes-brd4","link_type":"related","strength":0.7,"evidence":"Wiki page for BRD4 related to experiment"},{"source_artifact_id":"wiki-proteins-hdac5-protein","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-genes-hdac10","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-ideas-payload-hdac6-modulation-therapy","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-hdac6","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-genes-hdac11","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-mechanisms-hdac-inhibitor-mechanism","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-genes-hdac1","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-proteins-hdac11-protein","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-genes-hdac8","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-entities-histone-deacetylase","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to experiment"},{"source_artifact_id":"wiki-proteins-hdac6","link_type":"related","strength":0.7,"evidence":"Wiki page for HDAC related to 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