concept

TDP-43 AGGREGATION

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TDP-43 AGGREGATION: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

60Connections

1Hypotheses

13Analyses

21Outgoing

39Incoming

0Experiments

16Debates

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💡 Concept Info

Name	TDP-43 AGGREGATION

Pathway Diagram

graph TD
    TDP_43_AGGREGATION["TDP-43 AGGREGATION"]
    TDP_43_AGGREGATION -->|"causes"| Neurodegeneration["Neurodegeneration"]
    TDP_43_AGGREGATION -->|"contributes to"| Als_Pathology["Als Pathology"]
    TDP_43_AGGREGATION -->|"contributes to"| Ftd_Pathology["Ftd Pathology"]
    TDP_43_AGGREGATION -->|"mediates"| TDP_43_Loss_Of_Function["TDP-43 Loss Of Function"]
    TDP_43_AGGREGATION -.biomarker for.-> Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
    TDP_43_AGGREGATION -->|"interacts"| TDP_43_Mislocalization["TDP-43 Mislocalization"]
    p38__MAPK_inhibition["p38alpha MAPK inhibition"] -->|"reduces"| TDP_43_AGGREGATION
    oxidative_stress["oxidative stress"] -->|"promotes"| TDP_43_AGGREGATION
    SUMO2_3_conjugation["SUMO2/3 conjugation"] -.protects against.-> TDP_43_AGGREGATION
    TARDBP["TARDBP"] -->|"involved_in"| TDP_43_AGGREGATION
    cAMP_PKA_Signaling["cAMP/PKA Signaling"] -->|"modulates"| TDP_43_AGGREGATION
    Loss_Of_ASRGL1["Loss Of ASRGL1"] -->|"causes"| TDP_43_AGGREGATION
    Oxidative_Stress["Oxidative Stress"] -->|"activates"| TDP_43_AGGREGATION
    ASRGL1["ASRGL1"] -->|"inhibits"| TDP_43_AGGREGATION

Outgoing (21)

Target	Relation	Type	Str
Amyotrophic Lateral Sclerosis	associated_with	disease	0.98
Neurodegeneration	causes	phenotype	0.95
Als Pathology	contributes_to	phenotype	0.93
Ftd Pathology	contributes_to	phenotype	0.93
TDP-43 Loss Of Function	mediates	phenotype	0.90
Amyotrophic Lateral Sclerosis	biomarker_for	disease	0.90
intron retention clearance	inhibits	process	0.90
TDP-43 Mislocalization	interacts_with	process	0.85
mitochondrial DNA release	associated_with	mechanism	0.85
mitochondrial_dysfunction	associated_with	mechanism	0.75
Neuronal Lipid Profile Alterations	correlates_with	mechanism	0.75
faster cognitive decline in AD	causes	phenotype	0.70
Autophagosome-lysosome Fusion	inhibits	phenotype	0.70
SNAP29	associated_with	gene	0.70
syntaxin-17	associated_with	protein	0.70
ferroptosis	activates	pathway	0.70
Alzheimer's disease	biomarker_for	disease	0.70
Ferroptosis markers	precedes	biomarker	0.70
neuronal viability	inhibits	process	0.70
GBA intron retention clearance	inhibits	process	0.70
heterotypic_aggregation	causes	phenotype	0.50

Incoming (39)

Source	Relation	Type	Str
oxidative stress	promotes	process	1.00
SUMO2/3 conjugation	protects_against	process	1.00
p38α MAPK inhibition	reduces	process	1.00
TARDBP	involved_in	protein	0.98
cAMP/PKA Signaling	modulates	pathway	0.95
Loss Of ASRGL1	causes	mechanism	0.95
ASRGL1	inhibits	gene	0.90
C9orf72 repeat expansion	causes	gene	0.90
TARDBP	causes	gene	0.90
TDP-43 hyperphosphorylation	causes	process	0.90
21209826	is required for	paper	0.90
35495061	is tied to	paper	0.90
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	gene	0.90
TDP-43 ASO programs	therapeutic_target_for	drug	0.90
Oxidative Stress	activates	process	0.90
Phase Separation	contributes_to	process	0.90
Phosphatidylserine	promotes	compound	0.88
Cardiolipin	promotes	compound	0.88
HSP70	inhibits	protein	0.85
Autophagy-Lysosome Pathway	involved_in	pathway	0.85
alzheimers	associated_with	disease	0.85
TDP-43 S409/S410 Phosphorylation	associated_with	process	0.85
Oxidative Stress	exacerbates	process	0.85
oxidative stress	causes	process	0.80
NUFIP2	contributes_to	protein	0.80
HSP70	degrades	protein	0.75
TARDBP phase separation	causes	process	0.70
HSP70	modulates	protein	0.70
G3BP1 stress granules	nucleates	process	0.70
Nuclear import defects	precedes	mechanism	0.70
Loss of RNA co-factors	causes	process	0.70
TFEB	regulates	protein	0.70
stress granules	associated_with	process	0.70
misfolded PrP	induces	protein	0.70
P38	enhances	gene	0.70
autophagy-lysosomal flux impairment	prevents	mechanism	0.70
C-terminal_frameshift_mutations	causes	gene	0.70
microglial_activation	associated_with	mechanism	0.65
TFEB	modulates	gene	0.50

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Cytosolic TDP-43 aggregation sequesters SNAP29 and syntaxin-	0.600	neurodegeneration	What are the neuron-specific effects of

Mentioning Analyses (13)

Scientific analyses that reference this entity

Cross-disease neurodegeneration mechanism synthesis

neurodegeneration | 2026-04-28 | 17 hypotheses Top: 0.828

How does the intron-retained RNA isoform mechanistically reduce glucocerebrosida

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.645

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

neurodegeneration | 2026-04-18 | 4 hypotheses Top: 0.538

What are the specific design principles for small molecules that can selectively

medicinal chemistry | 2026-04-10 | 0 hypotheses

How can subcellular compartmentalization defects be measured as biomarkers in li

neuroscience | 2026-04-10 | 5 hypotheses Top: 0.724

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (16)

Multi-agent debates referencing this entity

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

closed · Rounds: 4 · Score: 0.72 · 2026-04-28

Debate: TREM2 Microglial Activation Rescues Amyloid Clearance in AD

closed · Rounds: 4 · Score: 0.75 · 2026-04-27

Hypothesis debate: C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

closed · Rounds: 4 · Score: 0.58 · 2026-04-27

Hypotheses created for system testing (hyp_test_* prefix)

closed · Rounds: 4 · Score: 0.77 · 2026-04-26

How does the intron-retained RNA isoform mechanistically reduce glucocerebrosida

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

The study shows stress granules are dynamic and reversible assemblies, but in ne

closed · Rounds: 4 · Score: 0.84 · 2026-04-22

The study shows that G3BP1 ubiquitination inhibits LLPS in vitro, but the molecu

closed · Rounds: 4 · Score: 0.79 · 2026-04-21

The abstract identifies APOE4 association with increased TDP-43 pathology but th

closed · Rounds: 4 · Score: 0.61 · 2026-04-21

TDP-43 inclusions occur in AD, ALS, and FTLD but the pathogenic mechanisms leadi

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

While ALS-causing mutations impair autophagy factors, the neuron-specific effect

closed · Rounds: 4 · Score: 0.81 · 2026-04-21

Related Research

Hypotheses and analyses mentioning TDP-43 AGGREGATION in their description or question text

No additional research found

TDP-43 AGGREGATION

Understanding Entity Pages

Pathway Diagram

Outgoing (21)

Incoming (39)

Targeting Hypotheses (1)

Mentioning Analyses (13)

Cross-disease neurodegeneration mechanism synthesis

How does the intron-retained RNA isoform mechanistically reduce glucocerebrosida

Is ferroptosis the primary driver of motor neuron death in ALS or an epiphenomen

What are the specific design principles for small molecules that can selectively

How can subcellular compartmentalization defects be measured as biomarkers in li

What are the neuron-specific effects of ALS-causing mutations on autophagy machi

What mechanisms drive TDP-43 pathology specifically in Alzheimer's disease versu

How does APOE4 mechanistically increase TDP-43 pathology frequency in Alzheimer'

How does TRIM21-mediated K63 ubiquitination of G3BP1 mechanistically inhibit liq

How do pathological stress granules transition from reversible to persistent in

TDP-43 phase separation therapeutics for ALS-FTD

RNA binding protein dysregulation across ALS FTD and AD

Test Hypothesis Fixtures

Experiments (0)

Related Papers (0)

Debates (16)

Which AD, PD, ALS, and FTD mechanisms recur across disease boundaries and yield

Debate: TREM2 Microglial Activation Rescues Amyloid Clearance in AD

Hypothesis debate: C9orf72 ASO Treatment Reverses TDP-43 Pathology in ALS/FTD

Hypotheses created for system testing (hyp_test_* prefix)

How does the intron-retained RNA isoform mechanistically reduce glucocerebrosida

The study shows stress granules are dynamic and reversible assemblies, but in ne

The study shows that G3BP1 ubiquitination inhibits LLPS in vitro, but the molecu

The abstract identifies APOE4 association with increased TDP-43 pathology but th

TDP-43 inclusions occur in AD, ALS, and FTLD but the pathogenic mechanisms leadi

While ALS-causing mutations impair autophagy factors, the neuron-specific effect

Related Research