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All 7 Hypotheses 1 Papers 1 Wikis 1 Gaps 1 Colliders 0 Debates 1 Bounties 0 Missions 1 Work packets 1 Genes 0 Diseases 0 Phenotypes 0 Gene ontology 0

+ Hypotheses 1 + Papers 1 ✓ Wikis 1 + Gaps 1 + Colliders 0 + Debates 1 + Bounties 0 + Missions 1 + Work packets 1 + Genes 0 + Diseases 0 + Phenotypes 0 + Gene ontology 0

30 results

Wiki Validated Hypothesis: p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43 Phosphorylation-Methylation Balance rel 6.19

TDP-43 hyperphosphorylation was established early in TDP-43 biology

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Wiki Validated Hypothesis: HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 Liquid-Liquid Phase Separation rel 4.45

TDP-43 Liquid-Liquid Phase Separation ## Scientific Rationale TDP-43

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Wiki TDP-43 Causal Weight Analysis: Motor-Neuron Loss in ALS and FTD-TDP rel 3.88

TDP-43^ΔNLS) that mislocalize TDP-43 without forcing aggregation

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Wiki Validated Hypothesis: Microglial AIM2 Inflammasome as the Primary Driver of TDP-43 Proteinopathy Neuroinflammation in ALS/FTD rel 2.54

TDP-43 Proteinopathy Neuroinflammation in ALS/FTD > **Status**: ✅ Validated | **Composite

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Wiki Validated Hypothesis: TDP-43 RNA-proteostasis failure across ALS, FTD, and AD/LATE rel 2.42

TDP-43 construct; quantify nuclear/cytoplasmic TDP-43, cryptic exon burden

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Wiki Validated Hypothesis: TIA1 Low-Complexity Domain Oxidation Drives Aberrant Stress Granule Assembly and TDP-43 Mislocalization in ALS Motor Neurons rel 2.39

TDP-43 aggregation, distinct from downstream strategies targeting established TDP

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Wiki Validated Hypothesis: RBM45 Liquid-Liquid Phase Separation Dominance Hijacks RNA Processing Condensates Toward Pathological Aggregation in ALS rel 1.64

TDP-43,TARDBP,hnRNP A1,HNRNPA1,phase separation,Liquid droplet

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Wiki Validated Hypothesis: STING Antagonists as ALS Therapeutics: Drug Repurposing rel 1.52

TDP-43 (TAR DNA-binding protein 43) pathology - a hallmark

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Wiki ALYREF rel 1.24

TDP-43 Burden"** (score: 0.58, disease: neurodegeneration). This hypothesis proposes

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Wiki Validated Hypothesis: SFPQ Paralog Displacement Triggers Cryptic Polyadenylation and Global RNA Stability Loss in ALS Motor Neurons rel 0.82

TDP-43 cytoplasmic mislocalization causes partial depletion of nuclear SFPQ

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Wiki Validated Hypothesis: TREM2-APOE microglial state switching across AD, ALS, and PD rel 0.71

TDP-43 neuroprotection; and PD microglia share the same damage

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Wiki Validated Hypothesis: Hypothesis 4: Metabolic Coupling via Lactate-Shuttling Collapse rel 0.70

TDP-43 and FUS into the nucleus. The importin-β/Ran-GTP

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Wiki Validated Hypothesis: Dual-Receptor Antibody Shuttling rel 0.61

TDP-43 pathology, the major proteinaceous inclusion in ALS, occurs

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Wiki Validated Hypothesis: Hypothesis 7: SST-SST1R/Gamma Entrainment-Enhanced Astrocyte Secretome rel 0.50

TDP-43 transgenic rats. Critical experiments include demonstrating direct causal

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Wiki Composite Claim: Sterile DAMP Sensing Primes Inflammasomes Across Neurodegenerative Contexts rel 0.41

TDP-43 proteinopathy is the chief upstream trigger. **Combined evidence

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Wiki Virginia M Y Lee rel 0.40

TDP-43 can adopt conformations that corrupt normal protein molecules

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Wiki Validated Hypothesis: pH-Sensitive Bispecific Antibody Targeting Transferrin Receptor for CNS Delivery rel 0.40

TDP-43 could address the heterogeneous pathology characteristic of advanced

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Wiki Validated Hypothesis: TBK1 Loss Locks Microglia in an Aged/Senescent Transcriptional State, Fueling ALS-Associated SASP rel 0.40

TDP-43 pathology can activate cGAS-STING signaling in ALS, implicating

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Wiki Protein Aggregation and Prion-like Spread Consensus rel 0.30

TDP-43, FUS, or other aggregate-prone proteins seed toxicity

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Wiki Validated Hypothesis: C9ORF72 autophagy-lysosome collapse across ALS and FTD rel 0.30

TDP-43 mislocalization, and cell-type survival. Cross-disease confidence

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Wiki Validated Hypothesis: hnRNP A2/B1 Staufen2-Mediated Axonal RNA Granule Transport Failure Drives Distal Axon Degeneration in ALS rel 0.30

TDP-43 axonal local synthesis and NMJ integrity in ALS motor

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Wiki Validated Hypothesis: GLE1-Mediated mRNA Export Defect Creates Translation-Competent mRNA Starvation in ALS Motor Neuron Axons rel 0.30

TDP-43, as it addresses the upstream mRNA export step

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Wiki Validated Hypothesis: ATM Kinase Hyperactivation Triggers DNA Damage Response Overflow and p53-Dependent Motor Neuron Apoptosis in ALS rel 0.30

TDP-43 aggregates; p53 S15 phosphorylation is similarly elevated, correlating

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Wiki Validated Hypothesis: eIF2α Phosphorylation Imbalance Creates Integrated Stress Response Overflow That Represses Axonal Protein Synthesis in ALS rel 0.30

TDP-43/FUS aggregates), oxidative stress, and ER stress creates

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Wiki Validated Hypothesis: NLRP3 inflammasome amplification across AD and PD proteinopathy rel 0.20

TDP-43, α-synuclein)? 4. What delivery route and modality

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Wiki Validated Hypothesis: SNCA conformer propagation across PD, DLB, and MSA rel 0.20

TDP-43, α-synuclein)? 4. What delivery route and modality

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Wiki Validated Hypothesis: MAPT tau seeding and release across AD, FTD, and PD-spectrum disease rel 0.20

TDP-43, α-synuclein)? 4. What delivery route and modality

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Wiki Validated Hypothesis: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration rel 0.20

TDP-43, α-synuclein)? 4. What delivery route and modality

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Wiki Validated Hypothesis: APOE-Dependent Autophagy Restoration rel 0.20

TDP-43, α-synuclein)? 4. What delivery route and modality

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Wiki Validated Hypothesis: TREM2-Mediated Astrocyte-Microglia Crosstalk in Neurodegeneration rel 0.20

TDP-43, α-synuclein)? 4. What delivery route and modality

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