protein

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

12Analyses

50Outgoing

50Incoming

Summary

TAR DNA-binding protein 43, an RNA/DNA-binding protein central to ALS, FTD, and AD pathology.

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🔬 Protein Info

Gene Symbol	TDP-43
Chromosome	1p36.2
Protein Family	Heterogeneous nuclear ribonucleoprotein (hnRNP) family
Primary Expression	TDP-43 is ubiquitously expressed with high neuronal expression; pathological aggregation primarily affects motor neurons, cortical neurons, and hippocampal neurons
Subcellular Localization	Nucleus (physiological), cytoplasm (disease)
Molecular Weight	43 kDa (414 amino acids)
Pathways	Amyloid Filaments, Cytoplasmic Accumulation, Isoaspartate Formation, NEURODEGENERATION, Nuclear Condensation
UniProt ID	Q13148
GeneCards	TDP-43
Human Protein Atlas	TDP-43
Primary Target	TDP-43 protein aggregates (cytoplasmic inclusions) including C-terminal fragments (CTFs, 25 kDa and 35 kDa species) and phosphorylated TDP-43 (pSer409/410) aggregates
E3 Ligase	CRBN (cereblon) - the same target exploited by immunomodulatory imide drugs (IMiDs)
Target Type	Molecular glue / Induced proximityducer (~400 Da)
Progressive Supranuclear Palsy (PSP)	Some cases show TDP-43 co-pathology
Corticobasal Degeneration (CBD)	TDP-43 present in ~50% of cases
Associated Diseases	ALS, ALS-FTD, ALS/FTLD, AMYOTROPHIC LATERAL SCLEROSIS, APOPTOSIS, AUTOPHAGY
Known Drugs/Compounds	UG-rich RNA sequences, RAPAMYCIN, RNA oligonucleotides, PROTAC, ASO, trehalose
Interactions	UBIQUITIN, STING, PINK1, CHMP2B, VALOSIN, OVERVIEW
KG Connections	1679 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

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

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

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

→

Pathway Diagram

graph TD
    TDP_43["TDP-43"]
    TDP_43 -->|"activates"| mitochondrial_permeability_tra["mitochondrial permeability transition pore"]
    TDP_43 -->|"causes"| mitochondrial_DNA["mitochondrial DNA"]
    TDP_43 -->|"activates"| NF__B["NF-kappaB"]
    TDP_43 -->|"activates"| mPTP["mPTP"]
    TDP_43 -->|"causes"| ALS["ALS"]
    TDP_43 -.biomarker for.-> frontotemporal_lobar_degenerat["frontotemporal lobar degeneration"]
    TDP_43 -->|"expressed in"| neuron["neuron"]
    TDP_43 -->|"regulates"| translation_fidelity["translation fidelity"]
    ANXA11["ANXA11"] -->|"interacts"| TDP_43
    CSNK1D["CSNK1D"] -->|"phosphorylates"| TDP_43
    progranulin["progranulin"] -->|"regulates"| TDP_43
    ALS -->|"interacts"| TDP_43
    TARDBP["TARDBP"] -->|"encodes"| TDP_43
    APOE4["APOE4"] -->|"activates"| TDP_43
    GGGGCC_repeat_RNA["GGGGCC repeat RNA"] -->|"regulates"| TDP_43
    NEAT1["NEAT1"] -->|"regulates"| TDP_43
    C9orf72["C9orf72"] -->|"regulates"| TDP_43
    MITOCHONDRIAL_DNA["MITOCHONDRIAL DNA"] -->|"activates"| TDP_43

Outgoing (1321)

Target	Relation	Type	Str
SREBF2	binds	gene	1.00
HMGCR	binds	gene	1.00
HMGCS1	binds	gene	1.00
LDLR	binds	gene	1.00
AGGREGATION	causes	process	1.00
oligomerization	regulates	process	1.00
RNA binding	regulates	process	1.00
STABILITY	regulates	process	1.00
NEAT1	regulates	gene	0.95
LC3ylation	regulates	process	0.95
UNC13A	regulates	gene	0.95
RNA Splicing	involved_in	process	0.95
Gene Expression	regulates	process	0.95
Ftld	involved_in	disease	0.95
Ftld	associated_with	disease	0.95
Ad	associated_with	disease	0.95
Mitochondrial DNA Release	associated_with	process	0.95
Frontotemporal Lobar Degeneration	associated_with	disease	0.95
Splicing Repression	regulates	process	0.95
Nuclear Condensation	involved_in	process	0.95
Cryptic Exon Splicing	inhibits	process	0.95
ALS-FTD	associated_with	disease	0.95
UG-rich RNA sequences	binds	compound	0.95
Alternative Splicing	regulates	process	0.95
UNC13A	inhibits	gene	0.95
Cryptic Exon Inclusion	inhibits	process	0.95
KCNQ2	regulates	gene	0.95
ALS/FTLD	associated_with	disease	0.95
mRNA Splicing	regulates	process	0.95
Cytoplasmic Aggregation	causes	phenotype	0.95
Nuclear Depletion	causes	phenotype	0.95
Aggregation	involved_in	process	0.95
Frontotemporal Lobar Degeneration	biomarker_for	disease	0.95
FTLD-TDP	associated_with	disease	0.95
Cryptic Splicing	regulates	process	0.95
TDP-43 K181E	associated_with	biomarker	0.95
RNA Dysregulation	causes	process	0.95
PKN1	regulates	gene	0.95
Tdp-43 Proteinopathies	involved_in	disease	0.95
Als	involved_in	disease	0.95
Als	associated_with	disease	0.95
Frontotemporal Dementia	causes	disease	0.95
FTLD	associated_with	disease	0.95
Neurodegeneration	involved_in	process	0.95
Rna Splicing	involved_in	process	0.95
Alzheimer'S Disease	biomarker_for	disease	0.95
Alzheimer'S Disease	associated_with	disease	0.95
Rna Splicing	modulates	process	0.95
Mis-splicing	mediates	process	0.93
Cytoplasmatic Mislocalization	involved_in	phenotype	0.93

Incoming (1293)

Source	Relation	Type	Str
TARDBP	associated_with	gene	1.00
p38α MAPK	phosphorylates	protein	1.00
SUMO2/3	conjugates	protein	1.00
14-3-3θ	interacts_with	protein	0.95
cAMP/PKA Signaling	regulates	pathway	0.95
Stress Granules	involved_in	cell_type	0.95
TAU	interacts_with	protein	0.95
FUS	interacts_with	gene	0.95
TREM2	interacts_with	protein	0.95
ASRGL1	regulates	gene	0.95
NEURON	interacts_with	cell_type	0.95
STEM CELLS	activates	cell_type	0.95
MOTOR NEURONS	inhibits	cell_type	0.95
FRONTOTEMPORAL DEMENTIA	interacts_with	disease	0.95
Stress	activates	phenotype	0.92
TDP-43 Aggregates	associated_with	protein	0.90
ANXA11	aggregates_with	protein	0.90
G4C2 Hexanucleotide Repeat Expansion	associated_with	mechanism	0.90
Loss Of Asrgl1	causes	mechanism	0.90
ASRGL1	substrate_of	protein	0.90
MAPK	phosphorylates	pathway	0.90
Hyperphosphorylation	modulates	process	0.85
Ubiquitination	modulates	process	0.85
Cleavage	modulates	process	0.85
CHMP7	modulates	protein	0.85
SRRM2	interacts_with	gene	0.85
NUFIP2	interacts_with	gene	0.85
TDP-43 Fibrils	phosphorylates	compound	0.85
Mistranslation	exacerbates	process	0.85
RNA oligonucleotides	targets	compound	0.85
Ubiquitin-Proteasome System	degrades	pathway	0.85
Rna Oligonucleotides	inhibits	compound	0.85
ATAXIN-2	interacts_with	protein	0.85
Oxidative Stress	activates	process	0.85
ASRGL1	degrades	gene	0.85
RNA	regulates	gene	0.85
RNA	activates	gene	0.85
RNA	interacts_with	gene	0.85
ANXA11	interacts_with	gene	0.80
CSNK1D	phosphorylates	gene	0.80
Stress Granules	mediates	process	0.80
STMN2	downregulates	gene	0.80
OPTN	co_localizes	protein	0.80
Cysteine Oxidation	associated_with	process	0.80
AMYLOID	interacts_with	protein	0.80
IPSC	activates	cell_type	0.80
FRONTOTEMPORAL DEMENTIA	regulates	disease	0.80
HNRNPC	regulates	gene	0.80
ASRGL1	interacts_with	protein	0.80
FMRP	mitigates_toxicity	protein	0.80

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 (12)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-14 | 2 hypotheses Top: 0.658

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

medicinal chemistry | 2026-04-10 | 0 hypotheses

What determines the selectivity and efficiency of intercellular transmission pat

neurodegeneration | 2026-04-08 | 0 hypotheses

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

neurodegeneration | 2026-04-08 | 0 hypotheses

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

neurodegeneration | 2026-04-08 | 0 hypotheses

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 (21)

Molecular Glue for TDP-43 Aggregate Clearance

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 (12)

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

RNA binding protein dysregulation across ALS FTD and AD

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 (21)

Molecular Glue for TDP-43 Aggregate Clearance

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 (12)

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

RNA binding protein dysregulation across ALS FTD and AD

TDP-43 phase separation therapeutics for ALS-FTD

TDP-43 phase separation therapeutics for ALS-FTD

Related Papers (20)