pathway

Tdp-43

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about Tdp-43: 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.

2614Connections

6Hypotheses

11Analyses

50Outgoing

50Incoming

Summary

Tdp-43 is a biological pathway involved in neurodegeneration research. Key relationships include: associated with, activates, causes. Associated with Aging, Alzheimer, Amyotrophic Lateral Sclerosis. Connected to 177 entities in the SciDEX knowledge graph.

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🔀 Pathway Info

Name	Tdp-43
Key Genes/Proteins	ATXN2
Related Diseases	motor neuron loss, protein aggregates, LATE, Aging, Amyotrophic Lateral Sclerosis

🔮 Predicted Structure: Tdp-43 — AlphaFold Q13148 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (20)

Knowledge base pages for this entity

cbs-psp-daily-action-plan

therapeutic · 30834 words

→

Personalized Treatment Plan — Atypical Parkinsonism (CBS/PSP)

therapeutic · 15794 words

→

AAV Gene Therapy for Neurodevelopmental Epilepsy — Competitive Landscape & Delivery Alternatives

therapeutic · 15567 words

→

Corticobasal Syndrome (CBS)

disease · 11374 words

→

Novel Therapy Index

idea · 10647 words

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Pathway Diagram

graph TD
    MITOCHONDRIAL_DNA["MITOCHONDRIAL DNA"] -->|"activates"| Tdp_43["Tdp-43"]
    MOTOR_NEURONS["MOTOR NEURONS"] -->|"activates"| Tdp_43["Tdp-43"]
    NF__B["NF-KappaB"] -->|"activates"| Tdp_43["Tdp-43"]
    MTDNA["MTDNA"] -->|"activates"| Tdp_43["Tdp-43"]
    style Tdp_43 fill:#1b5e20,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1321)

Target	Relation	Type	Str
RNA splicing	regulates	process	0.92
motor neuron loss	causes	phenotype	0.90
protein aggregates	contributes_to	phenotype	0.90
LATE	implicated_in	disease	0.90
Protein aggregation	drives	process	0.90
motor neuron degeneration	drives	process	0.88
RNA processing	regulates	process	0.85
Endosome damage	causes	process	0.80
Dopaminergic cells	causes	cell_type	0.75
Aging	activates	disease	0.60
Amyotrophic Lateral Sclerosis	associated_with	disease	0.60
Als	activates	disease	0.60
Neurodegeneration	activates	disease	0.60
Parkinson	associated_with	disease	0.60
Als	associated_with	disease	0.60
Huntington	associated_with	disease	0.60
Amyotrophic Lateral Sclerosis	phosphorylates	disease	0.60
Alzheimer	expressed_in	disease	0.60
Als	expressed_in	disease	0.60
Frontotemporal Dementia	activates	disease	0.60
Dementia	activates	disease	0.60
Aging	encodes	disease	0.60
Neurodegeneration	encodes	disease	0.60
Als	encodes	disease	0.60
Frontotemporal Dementia	associated_with	disease	0.60
Dementia	associated_with	disease	0.60
Amyotrophic Lateral Sclerosis	therapeutic_target	disease	0.60
Als	inhibits	disease	0.60
Als	therapeutic_target	disease	0.60
Alzheimer	inhibits	disease	0.60
Stroke	inhibits	disease	0.60
Neuroinflammation	inhibits	disease	0.60
Dementia	therapeutic_target	disease	0.60
Frontotemporal Dementia	therapeutic_target	disease	0.60
Aging	therapeutic_target	disease	0.60
Amyotrophic Lateral Sclerosis	inhibits	disease	0.60
Neurodegeneration	regulates	disease	0.60
Neurodegeneration	therapeutic_target	disease	0.60
Aging	inhibits	disease	0.60
Neurodegeneration	contributes_to	disease	0.60
Neurodegeneration	interacts_with	disease	0.60
Als	degrades	disease	0.60
Amyotrophic Lateral Sclerosis	activates	disease	0.60
Neurodegeneration	inhibits	disease	0.60
Amyotrophic Lateral Sclerosis	contributes_to	disease	0.60
Frontotemporal Dementia	interacts_with	disease	0.60
Dementia	interacts_with	disease	0.60
Amyotrophic Lateral Sclerosis	encodes	disease	0.60
Als	interacts_with	disease	0.60
Neurodegeneration	biomarker_for	disease	0.60

Incoming (1293)

Source	Relation	Type	Str
ATXN2	suppresses	gene	0.95
Phosphatidylserine	promotes	compound	0.85
Cardiolipin	promotes	compound	0.85
MITOCHONDRIAL DNA	activates	gene	0.60
MOTOR NEURONS	activates	gene	0.60
NF-ΚB	activates	gene	0.60
MTDNA	activates	gene	0.60
DNA	causes	gene	0.60
IFN	activates	gene	0.60
MITOCHONDRIA	causes	gene	0.60
CGAS	activates	gene	0.60
ALS	activates	gene	0.60
INFLAMMATION	causes	gene	0.60
STING	activates	gene	0.60
AMYOTROPHIC LATERAL SCLEROSIS	associated_with	gene	0.60
TREHALOSE	activates	gene	0.60
MTOR	associated_with	gene	0.60
P62	associated_with	gene	0.60
DNA	associated_with	gene	0.60
TPP1	associated_with	gene	0.60
PPP3	associated_with	gene	0.60
SOD1	associated_with	gene	0.60
TREH	associated_with	gene	0.60
PARKINSON	associated_with	gene	0.60
STUB1	associated_with	gene	0.60
ATG	associated_with	gene	0.60
STIP1	associated_with	gene	0.60
SQSTM1	associated_with	gene	0.60
NEURODEGENERATIVE DISEASES	associated_with	gene	0.60
GAPDH	associated_with	gene	0.60
ALS	associated_with	gene	0.60
CTSB	associated_with	gene	0.60
PPP3CB	associated_with	gene	0.60
NEURODEGENERATION	activates	gene	0.60
ATG10	activates	gene	0.60
HUNTINGTON	associated_with	gene	0.60
GLA	associated_with	gene	0.60
LAMP1	associated_with	gene	0.60
HSPA8	associated_with	gene	0.60
TARDBP	associated_with	gene	0.60
MAP1LC3B	associated_with	gene	0.60
LGALS3	associated_with	gene	0.60
ATG12	activates	gene	0.60
BECN1	associated_with	gene	0.60
HSPB8	associated_with	gene	0.60
LAMP2A	associated_with	gene	0.60
TFEB	associated_with	gene	0.60
PPARGC1A	associated_with	gene	0.60
BAG3	associated_with	gene	0.60
MCOLN1	associated_with	gene	0.60

Targeting Hypotheses (6)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
STMN2 Restoration as a Prerequisite for Axon Growth After TD	0.658	neurodegeneration	What molecular mechanisms enable functio
p38α Inhibitor and PRMT1 Activator Combination to Restore Ph	0.615	neurodegeneration	What is the therapeutic window between i
Microglial AIM2 Inflammasome as the Primary Driver of TDP-43	0.601	neurodegeneration	What are the mechanisms by which gut mic
HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43	0.598	neurodegeneration	What is the therapeutic window between i
TDP-43 Cryptic Exon–Targeted ASOs to Restore Hippocampal Gam	0.577	neurodegeneration	RNA binding protein dysregulation across

RNA-Binding Competition Therapy for TDP-43 Cross-Seeding	0.374	neurodegeneration	Protein aggregation cross-seeding across

Mentioning Analyses (11)

Scientific analyses that reference this entity

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
TDP-43 Pathology in Alzheimer's Disease. [PMID:34930382]	Meneses A, Koga S, O'Leary J, Dickson DW	Mol Neurodegener	2021	2
Protein transmission in neurodegenerative disease. [PMID:32203399]	Peng C, Trojanowski JQ, Lee VM	Nat Rev Neurol	2020	2
TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS [PMID:33031745]	Yu CH, Davidson S, Harapas CR, Hilton JB	Cell	2020	2
ALS-related proteinopathies: From TDP-43 to mitochondrial proteinopathies. [PMID:41570741]	Genin EC, Paquis-Flucklinger V	Current opinion in neurobiolog	2026	0
Refolding-assisted purification of native full-length TDP-43 compatible with BSL [PMID:41692368]	Dehury S, Tiwari S, Los Rios P	Methods	2026	0
Small heat shock proteins HspB1 and HspB5 differentially alter the condensation [PMID:41854301]	Walker TB, Trowbridge JW, McMahon S, Mar	Protein Sci	2026	0
Structural and Mechanistic Heterogeneity of the Phase Separation and Aggregation [PMID:41871974]	Doke AA, Kirmire MS, Jha A, Jha SK	ACS Chem Neurosci	2026	0
The Genetics of TDP-43 Type C Neurodegeneration: A Whole-Genome Sequencing Study [PMID:41883703]	Nassan M, Ayala I, Sloan J, Bonfitto A,	Neurology. Genetics	2026	0
Circular RNAs from the MAPT and TARDBP genes: Novel players in neurodegeneration [PMID:40633584]	["Bagheri N", "Margvelani G", "Chiang T"	Neurochemistry international	2025	0
Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-4 [PMID:40252666]	Balendra R, Sreedharan J, Hallegger M, L	The Lancet. Neurology	2025	0
Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine meth [PMID:39817908]	Aikio M, Odeh HM, Wobst HJ, Lee BL, Chan	Cell Rep	2025	0
Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via [PMID:39936620]	Ding N, Song Y, Zhang Y, Yu W, Li X et a	Autophagy	2025	0
Reactive astrocytes secrete the chaperone HSPB1 to mediate neuroprotection. [PMID:38507480]	Yang F, Beltran-Lobo P, Sung K, Goldrick	Sci Adv	2024	0
crVDAC3 alleviates ferroptosis by impeding HSPB1 ubiquitination and confers tras [PMID:39243601]	Zou Y, Yang A, Chen B, Deng X, Xie J et	Drug Resist Updat	2024	0
HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell dea [PMID:37454220]	Liang Y, Wang Y, Zhang Y, Ye F, Luo D et	Cell Death Dis	2023	0
Integrating single-nucleus sequence profiling to reveal the transcriptional dyna [PMID:37735671]	Fan LY, Yang J, Liu RY, Kong Y, Guo GY e	J Transl Med	2023	0
TREM2 interacts with TDP-43 and mediates microglial neuroprotection against TDP- [PMID:34916658]	Xie M, Liu YU, Zhao S, Zhang L, Bosco DB	Nature neuroscience	2022	0
Magnetic control of tokamak plasmas through deep reinforcement learning. [PMID:35173339]	Degrave J, Felici F, Buchli J, Neunert M	Nature	2022	0
Identification of energy metabolism-related biomarkers for risk prediction of he [PMID:36304554]	Chen H, Jiang R, Huang W, Chen K, Zeng R	Front Cardiovasc Med	2022	0
Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Exp [PMID:35302338]	Ganassi M, Zammit PS	Eur J Transl Myol	2022	0

Tdp-43

Understanding Entity Pages

Summary

Wiki Pages (20)

cbs-psp-daily-action-plan

Personalized Treatment Plan — Atypical Parkinsonism (CBS/PSP)

AAV Gene Therapy for Neurodevelopmental Epilepsy — Competitive Landscape & Delivery Alternatives

Corticobasal Syndrome (CBS)

Novel Therapy Index

Pathway Diagram

Outgoing (1321)

Incoming (1293)

Targeting Hypotheses (6)

Mentioning Analyses (11)

What molecular mechanisms enable functional recovery and muscle re-innervation a

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

What determines the selectivity and efficiency of intercellular transmission pat

What mechanisms underlie TDP-43's contribution to cognitive impairment severity

What upstream mechanisms cause TDP-43 to trigger mPTP opening and can this be th

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

How does chronic cGAS/STING activation downstream of TDP-43 contribute to progre

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

What determines the specificity of TDP-43-induced mitochondrial DNA release for

TDP-43 phase separation therapeutics for ALS-FTD

TDP-43 phase separation therapeutics for ALS-FTD

Related Papers (20)

Tdp-43

Understanding Entity Pages

Summary

Wiki Pages (20)

cbs-psp-daily-action-plan

Personalized Treatment Plan — Atypical Parkinsonism (CBS/PSP)

AAV Gene Therapy for Neurodevelopmental Epilepsy — Competitive Landscape & Delivery Alternatives

Corticobasal Syndrome (CBS)

Novel Therapy Index

Parkinson's Disease

Microglia CD8+ T Cell Recruitment -- Supplementary WW Content

primary-progressive-aphasia

Parthanatos in Neurodegeneration

calcium-dysregulation-comparison

Myoclonus and Cortical Hyperexcitability in Corticobasal Syndrome

nimodipine-als

Neuroresilience Mechanisms and Evidence

Therapeutics

NPM1 Gene

Section 162: Advanced Antioxidant and Redox Therapy in CBS/PSP

Frontotemporal Dementia (FTD) Mechanistic Pathway

neuroinflammation

GRIA3 Gene

Frontotemporal Dementia (FTD)

Pathway Diagram

Outgoing (1321)

Incoming (1293)

Targeting Hypotheses (6)

Mentioning Analyses (11)

What molecular mechanisms enable functional recovery and muscle re-innervation a

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

What determines the selectivity and efficiency of intercellular transmission pat

What mechanisms underlie TDP-43's contribution to cognitive impairment severity

What upstream mechanisms cause TDP-43 to trigger mPTP opening and can this be th

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

How does chronic cGAS/STING activation downstream of TDP-43 contribute to progre

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

What determines the specificity of TDP-43-induced mitochondrial DNA release for

TDP-43 phase separation therapeutics for ALS-FTD

TDP-43 phase separation therapeutics for ALS-FTD

Related Papers (20)