🧫

Mechanism: Progranulin Loss and TDP-43 Pathology in FTD

experiment Created: 2026-04-02T17:01:41 By: crosslink-v2 Quality: 67% ✓ SciDEX ID: experiment-exp-wiki-experiments-progranu
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Metadata
experiment_typevalidation
source{'type': 'manual', 'source_name': 'wiki', 'extraction_date': '2026-04-16T01:00:16.900227Z', 'extracted_by': 'backfill_v1'}
entities{'genes': ['TDP'], 'diseases': ['ALS']}
model_systemhuman
summary# Mechanism: Progranulin Loss and TDP-43 Pathology in FTD ## Background and Rationale Frontotemporal dementia (FTD) represents the second most common early-onset dementia, with heterozygous mutations
replication_statussingle_study
methodology_notesPhase 1: Post-mortem tissue analysis (Weeks 1-8). Collect frozen frontal/temporal cortex samples from GRN mutation carriers (n=20), sporadic FTD cases (n=20), and age-matched controls (n=15). Perform
primary_outcomeValidate Mechanism: Progranulin Loss and TDP-43 Pathology in FTD
extraction_metadata{'extraction_confidence': 0.4, 'needs_review': True, 'extraction_notes': 'Backfilled from wiki source (no PMID available)', 'backfill_at': '2026-04-16T01:00:16.900232'}
🌍 Provenance Graph 9 nodes, 30 edges

derives from (16)

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supports (5)

Linked Artifacts (1096)
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mentions📖als100%
derives_from📖Mechanism: Progranulin Loss and TDP-43 Pathology in FTD95%
derives_from🧪Cryptic Exon Silencing Restoration90%
derives_from🧪Glycine-Rich Domain Competitive Inhibition90%
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derives_from🧪Cross-Seeding Prevention Strategy90%
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mentions📖Guam Parkinsonism-Dementia Complex (ALS-PDC)55%
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mentions📖Progressive Supranuclear Palsy - Richardson Syndrome55%
mentions📖Progressive Supranuclear Palsy (PSP)55%
mentions📖Cognitive Impairment in Progressive Supranuclear Palsy55%
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mentions📖Genetics of Progressive Supranuclear Palsy55%
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related📖AAN 2026 Clinical Trials54%
related📖CTAD 2026 — Clinical Trials on Alzheimer's Disease54%
related📖PD Clinical Trials — MDS 202654%
related📖mTOR Signaling Dysregulation in Progressive Supranuclear Pal54%
related📖SfN 2026: ALS and Motor Neuron Disease Sessions54%
related📖AD Amyloid-Resilient Phenotype Study — Why Some amyloid-Posi54%
related📖Metabolic Pathway-Targeted Therapy in ALS54%
related📖Sporadic ALS Initiation Biology: Deep Phenotyping of At-Risk54%
related📖Anti-Tau Therapy Failure Mechanism in PSP — Why Clinical Tri54%
related📖c9orf72-als-ftd-phenotype-mechanism54%
related📖Mechanism: C9orf72 Hexanucleotide Repeat Expansion in ALS/FT54%
related📖C9orf72 Phenotype Divergence: ALS vs FTD Mechanism Study54%
related📖Environmental Exposure Causal Attribution in ALS — Experimen54%
related📖Microbiome-Gut Barrier Signatures in ALS — Experiment Design54%
related📖Sleep and Respiratory Network Interaction in ALS — Experimen54%
related📖Viral and Post-Infectious Mechanisms in ALS — Experiment Des54%
related📖ALS10 - Amyotrophic Lateral Sclerosis 10 (TARDBP)54%
related📖ALS2 (Alsin)54%
related📖als454%
related📖ALS7 - Amyotrophic Lateral Sclerosis 754%
related📖ALS8 - Amyotrophic Lateral Sclerosis 854%
related📖ALS9 - Amyotrophic Lateral Sclerosis 954%
related📖Alsin (ALSIN)54%
related📖ALSINC — ALS IncRNA54%
related📖Calsyntenin 154%
related📖LGALS1 — Galectin-154%
related📖LGALS3 Gene54%
related📖TBK1-Mediated Neuroinflammation Hypothesis — Autophagy Failu54%
related📖FUS Protein-Targeting Therapy for ALS/FTD54%
related📖VCP Proteostasis Modulation Therapy for ALS/FTD54%
related📖CurePSP - Foundation for Progressive Supranuclear Palsy54%
related📖Healey Center for ALS54%
related📖Linked Clinical Trials (Cure Parkinson's)54%
related📖Linked Clinical Trials Program54%
related📖Shanghai Pharmaceuticals54%
related📖Amyotrophic Lateral Sclerosis (ALS) Investment Landscape54%
related📖Progressive Supranuclear Palsy (PSP) Investment Landscape54%
related📖Progressive Supranuclear Palsy Investment Landscape54%
related📖C9orf72 Hexanucleotide Repeat Expansion Pathway in ALS54%
related📖Ion Channel Dysfunction in ALS54%
related📖SOD1 ALS Pathway54%
related📖Astrocyte Dysfunction: AD vs PD vs ALS vs FTD vs HD Comparis54%
related📖Autophagy Dysfunction in Progressive Supranuclear Palsy54%
related📖Autophagy Failure Comparison -- AD/PD/ALS/FTD/HD54%
related📖Autophagy-Lysosomal Impairment Comparison — AD/PD/ALS/FTD/HD54%
related📖Axonal Transport Dysfunction in Progressive Supranuclear Pal54%
related📖Blood-Brain Barrier Dysfunction: AD vs PD vs ALS Comparison54%
related📖C9orf72-ALS Network54%
related📖C9orf72 Hexanucleotide Repeat Expansion Pathway in ALS and F54%
related📖C9orf72→RNA/Dipeptide Repeat Pathology→ALS/FTD — Causal Chai54%
related📖Calcium Dysregulation in Progressive Supranuclear Palsy54%
related📖CHCHD10 Mitochondrial Dysfunction — ALS/FTD Causal Chain54%
related📖Computational Models of Tau Propagation in Progressive Supra54%
related📖Computational Tau Spreading Models in Progressive Supranucle54%
related📖Cytoskeleton Dysfunction Comparison -- AD/PD/ALS/FTD/HD54%
related📖Dipeptide Repeat Proteins (DPRs) in C9orf72-ALS/FTD54%
related📖Epigenetic Dysregulation Comparison -- AD/PD/ALS/FTD/HD54%
related📖Epigenetics in Amyotrophic Lateral Sclerosis54%
related📖Epigenetic Changes in Progressive Supranuclear Palsy54%
related📖ER Stress and Unfolded Protein Response in Progressive Supra54%
related📖Exosome-Mediated Tau Propagation in Progressive Supranuclear54%
related📖Ferroptosis Disease Comparison — AD/PD/ALS/FTD/HD54%
related📖FUS Gene-Mechanism-Therapy Causal Chain — ALS/FTD54%
related📖FUS Proteinopathy Pathway in ALS54%
related📖Heat Shock Protein Dysfunction in Progressive Supranuclear P54%
related📖Iron Accumulation in Progressive Supranuclear Palsy54%
related📖Lipid Metabolism Dysfunction Comparison — AD/PD/ALS/FTD/HD54%
related📖Lysosomal Dysfunction in Progressive Supranuclear Palsy54%
related📖Metabolomic Alterations in Progressive Supranuclear Palsy54%
related📖Microglia Dysfunction: AD vs PD vs ALS vs FTD vs HD Comparis54%
related📖mitochondrial-dysfunction-als54%
related📖Mitochondrial Dysfunction in ALS-FTD Spectrum54%
related📖Motor Neuron Vulnerability in ALS54%
related📖mTOR Signaling Dysregulation in Progressive Supranuclear Pal54%
related📖Myelin Pathology Disease Comparison — AD/PD/ALS/FTD/HD54%
related📖Myelin Pathology in Progressive Supranuclear Palsy54%
related📖neuroinflammation-ad-pd-als54%
related📖Neuroinflammation Comparison — AD/PD/ALS/FTD/HD54%
related📖Neuroinflammation Across AD, PD, ALS, FTD, and HD54%
related📖Neuroinflammation in Progressive Supranuclear Palsy54%
related📖Neuromelanin Loss in Progressive Supranuclear Palsy54%
related📖Neurotransmitter Dysfunction in Progressive Supranuclear Pal54%
related📖Neurovascular Coupling Disease Comparison — AD/PD/ALS/FTD/HD54%
related📖Non-Cell-Autonomous Glial Pathways in ALS54%
related📖Oligodendrocyte Dysfunction: AD vs PD vs ALS vs FTD vs HD Co54%
related📖Oligodendroglial Involvement in Progressive Supranuclear Pal54%
related📖OPTN (Optineurin) Mitophagy Dysfunction — ALS/FTD/PD Causal 54%
related📖PGC-1α Mitochondrial Biogenesis Comparison — AD/PD/ALS/FTD/H54%
related📖Pre-symptomatic Conversion Windows in ALS Genetic Risk Carri54%
related📖progressive-supranuclear-palsy-tauopathy54%
related📖Proteasome Dysfunction in Progressive Supranuclear Palsy54%
related📖Animal Models in Progressive Supranuclear Palsy Research54%
related📖Assistive Technology and Devices for Progressive Supranuclea54%
related📖Astrocytic Pathology in Progressive Supranuclear Palsy54%
related📖Autonomic Dysfunction in Progressive Supranuclear Palsy54%
related📖Brain Network Connectivity Changes in Progressive Supranucle54%
related📖Brainstem Reflex Dysfunction in Progressive Supranuclear Pal54%
related📖Central Vestibular Pathway Vulnerability in Progressive Supr54%
related📖Circadian Dysfunction and Melatonin Alterations in Progressi54%
related📖Cortical Involvement and Neurodegeneration in Progressive Su54%
related📖Disease Progression and Staging in Progressive Supranuclear 54%
related📖Environmental Risk Factors in Progressive Supranuclear Palsy54%
related📖Gait and Balance Disorders in Progressive Supranuclear Palsy54%
related📖Metabolic Dysfunction and Insulin Resistance in Progressive 54%
related📖Mitochondrial Complex I Dysfunction in Progressive Supranucl54%
related📖Mitochondrial Dysfunction in Progressive Supranuclear Palsy54%
related📖Neuropathology of Progressive Supranuclear Palsy54%
related📖Noradrenergic Dysfunction in Progressive Supranuclear Palsy54%
related📖Ocular Motor Dysfunction in Progressive Supranuclear Palsy54%
related📖Olfactory Dysfunction in Progressive Supranuclear Palsy54%
related📖Pain Syndromes in Progressive Supranuclear Palsy54%
related📖Progressive Supranuclear Palsy (PSP) Pathway54%
related📖Perineuronal Net Dysfunction in Progressive Supranuclear Pal54%
related📖Proteomics of Progressive Supranuclear Palsy54%
related📖Pupillary and Visual Dysfunction in Progressive Supranuclear54%
related📖Pyroptosis and Inflammasome Activation in Progressive Supran54%
related📖Rehabilitation and Management of Progressive Supranuclear Pa54%
related📖Sleep and Circadian Disorders in Progressive Supranuclear Pa54%
related📖Sleep-Disordered Breathing in Progressive Supranuclear Palsy54%
related📖Spatial Transcriptomics of Progressive Supranuclear Palsy54%
related📖Speech and Swallowing Disorders in Progressive Supranuclear 54%
related📖Speech and Voice Disorders in Progressive Supranuclear Palsy54%
related📖Tau Aggregate Specificity in Progressive Supranuclear Palsy54%
related📖Tau Oligomer Biology in Progressive Supranuclear Palsy54%
related📖Progressive Supranuclear Palsy Treatment Landscape54%
related📖Vestibular Dysfunction in Progressive Supranuclear Palsy54%
related📖Vestibular-Ocular Reflex Deficits in Progressive Supranuclea54%
related📖Veterinary Tauopathies in Progressive Supranuclear Palsy Res54%
related📖PTPσ (PTPRS) in C9ORF72-ALS/FTD - PI3P Regulation Mechanism54%
related📖Ribosomal and Translation Dysfunction in Progressive Supranu54%
related📖Selective Neuronal Vulnerability in Progressive Supranuclear54%
related📖SOD1 Superoxide Dismutase 1 ALS Causal Chain54%
related📖Sporadic ALS Initiation Mechanisms54%
related📖Stress Granule Homeostasis in ALS/FTD54%
related📖Synaptic Dysfunction in Progressive Supranuclear Palsy54%
related📖Tau Aggregation Mechanisms in Progressive Supranuclear Palsy54%
related📖Tau Propagation and Seeding in Progressive Supranuclear Pals54%
related📖Exosome-Mediated Tau Propagation in Progressive Supranuclear54%
related📖TBK1 Autophagy and Neuroinflammation ALS/FTD Causal Chain54%
related📖TBK1-Mediated Neuroinflammation Hypothesis — Impaired Autoph54%
related📖TREM2 in ALS54%
related📖Vascular and Endothelial Dysfunction in Progressive Supranuc54%
related📖viral-post-infectious-als54%
related📖als254%
related📖ALS2 Protein (Alsin)54%
related📖ALS4 Protein (Alsin)54%
related📖ALS4 Protein (Alsine)54%
related📖Alsin Protein (ALS2)54%
related📖Alsin Protein54%
related📖ALSINC Protein - ALS IncRNA54%
related📖LGALS1 Protein — Galectin-154%
related📖lgals3-protein54%
related📖Patricia Martinez — PSP Clinical Trials Researcher54%
related📖BCI Clinical Trials for Neurodegenerative Diseases54%
related📖Brain-Computer Interface for Progressive Supranuclear Palsy54%
related📖Failed Alzheimer's Disease Clinical Trials Analysis54%
related📖ALSENLITE: Senolytics for Alzheimer's Disease Trial54%
related📖Treatment Approaches for Amyotrophic Lateral Sclerosis (ALS)54%
related📖Amyotrophic Lateral Sclerosis (ALS) Treatment54%
related📖Anti-Amyloid Antibody Clinical Trials54%
related📖Antisense Oligonucleotide Therapy for C9orf72 ALS/FTD54%
related📖CBS/PSP Clinical Trials Guide54%
related📖Emerging Clinical Trials in Neurodegenerative Diseases54%
related📖Progressive Supranuclear Palsy (PSP) Treatment54%
related📖Progressive Supranuclear Palsy (PSP) Treatment Guide54%
related📖Promising Clinical Trials in Neurodegenerative Diseases54%
related📖Sodium Phenylbutyrate/Taurursodiol (Relyvrio) for ALS54%
related📖Relyvrio (Sodium Phenylbutyrate/Taurursodiol) for ALS54%
related📖Senolytic Therapies for CBS and [PSP](/diseases/progressive-54%
related📖SOD1-Targeting Therapies for ALS54%
related📖Valproic Acid Trial Failure in Progressive Supranuclear Pals54%
mentions📖GRN — Progranulin50%
mentions📖Lysosomal Associated Membrane Protein 1 (LAMP1)50%
mentions📖Progranulin (PGRN)50%
related📖HNRPU — Heterogeneous Nuclear Ribonucleoprotein U45%
mentions📖p62/SQSTM1 (Sequestosome-1)40%
mentions📖upr40%
mentions📖VIRMA (KIAA1429)40%
mentions📖ALS8 - Amyotrophic Lateral Sclerosis 840%
mentions📖ALS9 - Amyotrophic Lateral Sclerosis 940%
mentions📖APE1 — AP Endonuclease 140%
mentions📖BAG440%
mentions📖CANX — Calnexin40%
mentions📖cct740%
mentions📖DDX55 (DEAD-Box Helicase 55)40%
mentions📖DHX36 — DEAH-Box Helicase 3640%
mentions📖DIABLO40%
mentions📖dnajc440%
mentions📖DYNC2H1 — Dynein Cytoplasmic 2 Heavy Chain 140%
mentions📖ERK2 (MAPK1)40%
mentions📖fip20040%
mentions📖GALNT2 — Polypeptide N-acetylgalactosaminyltransferase 240%
mentions📖gemin440%
mentions📖HNRNPA1 - Heterogeneous Nuclear Ribonucleoprotein A140%
mentions📖HSPA640%
mentions📖KDM6B (JMJD3)40%
mentions📖MAPT Haplotypes (H1/H2)40%
mentions📖MEF2D — Myocyte Enhancer Factor 2D40%
mentions📖mief140%
mentions📖MSH2 — MutS Homolog 240%
mentions📖NCL — Nucleolin40%
mentions📖PACRG40%
mentions📖pdia140%
mentions📖PRPF3 — Pre-mRNA Processing Factor 340%
mentions📖PSMB940%
mentions📖PSMC1 (Proteasome 26S Subunit ATPase 1)40%
mentions📖PUM2 — Pumilio RNA Binding Family Member 240%
mentions📖BBC3 — BCL2 Binding Component 3 (PUMA)40%
mentions📖RNA Binding Fox-1 Homolog 2 (RBFOX2)40%
mentions📖RNASEH1 — Ribonuclease H140%
mentions📖RPA340%
mentions📖RPL2640%
mentions📖slc17a940%
mentions📖SLC30A140%
mentions📖SS18L1 (CREST) (SS18L1)40%
mentions📖STX10 — Syntaxin 1040%
mentions📖SURF6 — SURF6 Homolog40%
mentions📖timm2240%
mentions📖TMEM173 (STING)40%
mentions📖tmx240%
mentions📖TPM1 — Tropomyosin 140%
mentions📖TRA2B — Transformer 2 Beta Homolog40%
mentions📖trim240%
mentions📖TYNDASE — Tyndall40%
mentions📖UBE2N40%
mentions📖ubqln240%
mentions📖UBQLN3 — Ubiquilin 340%
mentions📖ubxd540%
mentions📖xpg40%
mentions📖ZNRNP1 — Zinc Finger, RNGTT Type 140%
mentions📖Cerebral Organoid Model40%
mentions📖als40%
mentions📖Progranulin (PGRN) - Biomarker40%
mentions📖Progranulin (PGRN)40%