TARDBP Protein (TDP-43)

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TARDBP Protein (TDP-43)

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TARDBP Protein (TDP-43)

Pathway Diagram

```mermaid
flowchart TD
TARDBP["TARDBP"]
style TARDBP fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0
TDP_43["TDP-43"]
TARDBP -->|"associated with"| TDP_43
DEMENTIA["DEMENTIA"]
TARDBP -->|"associated with"| DEMENTIA
FRONTOTEMPORAL_DEMENTIA["FRONTOTEMPORAL DEMENTIA"]
TARDBP -->|"associated with"| FRONTOTEMPORAL_DEMENTIA
Amyotrophic_Lateral_Sclerosis["Amyotrophic Lateral Sclerosis"]
TARDBP -->|"risk factor for"| Amyotrophic_Lateral_Sclerosis
NEURON["NEURON"]
TARDBP -->|"associated with"| NEURON
Als["Als"]
TARDBP -->|"associated with"| Als
RPTOR["RPTOR"]
TARDBP -->|"regulates"| RPTOR
FTD["FTD"]
TARDBP -->|"associated with"| FTD
FUS["FUS"]
FUS -->|"associated with"| TARDBP
ALS["ALS"]
ALS -->|"associated with"| TARDBP
NEURODEGENERATION["NEURODEGENERATION"]
NEURODEGENERATION -->|"associated with"| TARDBP
SOD1["SOD1"]
SOD1 -->|"associated with"| TARDBP
h_7e846ceb["h-7e846ceb"]
h_7e846ceb -->|"therapeutic target"| TARDBP
h_4fabd9ce["h-4fabd9ce"]
h_4fabd9ce -->|"therapeutic target"| TARDBP
h_eea667a9["h-eea667a9"]
h_eea667a9 -->|"therapeutic target"| TARDBP
h_7e846ceb -->|"targets gene"| TARDBP
style TDP_43 fill:#4a1a6b,stroke:#ce93d8,color:#e0e0e0
style DEMENTIA fill:#ef5350,stroke:#ef5350,color:#e0e0e0
style FRONTOTEMPORAL_DEMENTIA fill:#ef5350,stroke:#ef5350,color:#e0e0e0
style Amyotrophic_Lateral_Sclerosis fill:#ef5350,stroke:#ef5350,color:#e0e0e0
style NEURON fill:#006494

...

TARDBP Protein (TDP-43)

Pathway Diagram

Mermaid diagram (expand to render)

Overview

TARDBP encodes TDP-43 (TAR DNA-binding protein of 43 kDa), a DNA/RNA-binding protein that is a major pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Abnormal aggregation of TDP-43 in cytoplasmic inclusions is a defining feature of approximately 95% of ALS cases and 50% of FTD cases. [@chenplotkin2023]

TDP-43 is a ubiquitously expressed nuclear protein with essential functions in RNA processing. The protein localizes predominantly to the nucleus in healthy cells but redistributes to the cytoplasm in disease states, forming characteristic inclusions that define a new class of proteinopathies. This pathology is found not only in ALS and FTD but also in many other neurodegenerative diseases, making TDP-43 a central player in neurodegeneration research. [@neumann2006] [@arai2006]

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#4477AA;color:white;">TDP-43 (TARDBP)</th></tr>
<tr><td>Gene</td><td>[TARDBP](/genes/tardbp)</td></tr>
<tr><td>UniProt ID</td><td>[Q13148](https://www.uniprot.org/uniprot/Q13148)</td></tr>
<tr><td>PDB ID</td><td>2N4P, 5W5N, 6N3B</td></tr>
<tr><td>Protein Length</td><td>414 amino acids</td></tr>
<tr><td>Molecular Weight</td><td>~43 kDa</td></tr>
<tr><td>Subcellular Localization</td><td>Nucleus (healthy), Cytoplasm (disease)</td></tr>
<tr><td>Expression</td><td>Ubiquitous; high in brain and spinal cord</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/als-therapeutic-landscape-—-programs-by-phase-and-modality" style="color:#ef9a9a">ALS Therapeutic Landscape — Programs by Phase and Modality</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a></td>
</tr>
<tr>
<td class="label">SciDEX Hypotheses</td>
<td><a href="/hypothesis/h-4fabd9ce" style="color:#ce93d8" title="Score: 0.46">Cryptic Exon Silencing Restoration...</a> <a href="/hypothesis/h-eea667a9" style="color:#ce93d8" title="Score: 0.45">Cross-Seeding Prevention Strategy...</a> <a href="/hypothesis/h-7693c291" style="color:#ce93d8" title="Score: 0.44">RNA-Binding Competition Therapy for TDP-...</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">670 edges</a></td>
</tr>
</table>
</div>

Molecular Biology and Structure

Protein Architecture

TDP-43 is a 414-amino acid protein with multiple functional domains:

N-Terminal Domain (1-76 aa):

Contains the nuclear localization signal (NLS)
Required for nuclear import
Mediates protein-protein interactions
Enables DNA binding

RNA Recognition Motif (RRM) Domain (106-262 aa):

Highly conserved RNA-binding domain
Recognizes (UG)n repeat sequences in RNA
Binds both DNA and RNA with similar affinity
Essential for most TDP-43 functions
Contains two RNP motifs (RNP1 and RNP2)

Glycine-Rich Domain (274-414 aa):

C-terminal region with low complexity
Prone to aggregation
Contains most disease-causing mutations (>50 known)
Mediates interactions with other RNA-binding proteins
Critical for protein solubility

Key Structural Features:

The RRM domain has a classic β-α-β-fold RNA-binding motif
The C-terminal domain is intrinsically disordered
Post-translational modifications (phosphorylation, ubiquitination) affect function
Forms multimers through C-terminal interactions

[@buratti2024]

Normal RNA Processing Functions

In the normal state, TDP-43 participates in numerous RNA processing functions:

1. Alternative Splicing:

Regulates inclusion/exclusion of exons
Influences splice site selection
Important for neuronal-specific splicing patterns
Targets include CFTR, tau, and neuronal transcripts

2. mRNA Stability:

Binds to 3' UTR regions
Affects mRNA decay rates
Regulates transcript stability
Involved in RNA quality control

3. RNA Transport:

Participates in mRNA trafficking to synapses
Localizes to dendritic compartments
Supports activity-dependent translation
Important for synaptic plasticity

4. Transcription Regulation:

Can act as transcriptional co-activator/repressor
Modulates gene expression
Interacts with transcriptional machinery

5. miRNA Processing:

Associates with Drosha complex
Affects miRNA biogenesis
Links to post-transcriptional regulation

6. Stress Response:

Transiently localizes to stress granules under cellular stress
Helps regulate stress-response mRNAs
Part of the cellular stress response machinery

[@lagier2009] [@da cruz2012]

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

ALS is a progressive neurodegenerative disease affecting upper and lower motor neurons. TDP-43 pathology is present in ~95% of ALS cases, making it the most common protein aggregate in this disease.

Pathology:

TDP-43 is the major constituent of cytoplasmic inclusions in motor [neurons](/entities/neurons)
Loss of nuclear TDP-43 and cytoplasmic accumulation is characteristic
Inclusions are ubiquitin-positive but tau-negative
Pathological phosphorylation at serine 409/410
Fragmentation of full-length TDP-43 into ~25-35 kDa fragments

Genetics:

Over 50 mutations in TARDBP cause familial and sporadic ALS
Mutations primarily in the C-terminal glycine-rich domain
Account for ~5% of familial ALS cases
Provide direct evidence that TDP-43 dysfunction causes disease
Include missense (e.g., A315T, G348C, Q331K) and truncation mutations

Pathogenic Mechanisms:
The precise mechanisms by which TDP-43 mutations cause disease remain under investigation:

Loss of nuclear function: Mutations may impair RNA processing, leading to altered splicing and expression of essential neuronal genes

Gain of toxic cytoplasmic function: Cytoplasmic aggregates may sequester essential proteins and RNAs

Stress granule dysregulation: Aberrant stress granule dynamics contribute to pathology

Mitochondrial dysfunction: TDP-43 affects mitochondrial gene expression

Excitotoxicity: Altered glutamate transporter expression may contribute

[@rutherford2008] [@kabashi2010] [@sreedharan2011] [@gao2018]

Frontotemporal Dementia (FTD)

FTD is a spectrum of neurodegenerative disorders characterized by progressive behavioral and language deficits. TDP-43 pathology is found in approximately 50% of FTD cases.

Pathology:

TDP-43 inclusions in neurons and glia of frontal and temporal cortices
Characteristic "type B" FTLD-TDP pathology
Neuronal loss and gliosis in affected regions
Subtypes based on distribution and pattern of inclusions

Spectrum Disease:

ALS-FTD overlap syndrome with TDP-43 pathology
Many patients show features of both conditions
Shared genetic and pathological mechanisms
Common in cases with C9orf72 expansions

Clinical Presentations:

Behavioral variant FTD (bvFTD)
Primary progressive aphasia (PPA)
Semantic variant PPA
Progressive nonfluent aphasia

[@neumann2022] [@li2018]

Alzheimer's Disease Co-Pathology

TDP-43 pathology is commonly observed in Alzheimer's disease:

Prevalence:

TDP-43 pathology observed in ~30-50% of AD cases
Often in limbic regions (hippocampus, amygdala)
More common with increasing AD severity
Often accompanies amyloid and tau pathology

Clinical Impact:

May contribute to cognitive decline beyond AD pathology
Associated with more rapid progression
Often in limbic regions
Can be a primary or secondary pathology

Relationship to AD:

Specific TDP-43 strains may differ from ALS/FTD
May interact with tau pathology
Role in disease progression actively studied

[@manchester2017]

Other Neurodegenerative Diseases

TDP-43 pathology is increasingly recognized in other conditions:

Parkinson's Disease:

TDP-43 inclusions in some cases
Often in older patients
May contribute to disease progression
Can be primary or secondary

Dementia with Lewy Bodies (DLB):

TDP-43 pathology in ~15-20% of cases
Often coexists with Lewy bodies
May affect clinical phenotype

Huntington's Disease:

TDP-43 co-pathology in some patients
May affect disease expression
Interaction with mutant huntingtin

Other Conditions:

Chronic traumatic encephalopathy
Some epilepsy cases
Inclusion body myositis

[@johansson2019]

Mechanisms of Pathogenesis

Nuclear Loss vs Cytoplasmic Gain

The fundamental question in TDP-43 proteinopathy is whether disease results from loss of nuclear function, gain of toxic cytoplasmic function, or both.

Loss of Nuclear Function Evidence:

Reduced nuclear TDP-43 in patient tissue
Mutations impair RNA binding
Altered splicing of target transcripts
Nuclear clearance mechanisms may contribute

Cytoplasmic Gain of Function Evidence:

Cytoplasmic inclusions are pathological hallmark
Overexpression of wild-type TDP-43 causes toxicity
Cytoplasmic TDP-43 disrupts mitochondrial function
Sequestration of essential RNAs in aggregates

The current consensus suggests both mechanisms contribute to disease, and therapeutic approaches may need to address both.

[@woerner2016] [@barmada2010]

Aggregation Mechanism

TDP-43 aggregation is central to disease pathogenesis:

Aggregation Process:

C-terminal domain drives aggregation
Low complexity region enables liquid-liquid phase separation
Pathological phosphorylation at S409/410 promotes aggregation
Truncation fragments seed aggregation
Prion-like spread between cells

Cell-to-Cell Transmission:

TDP-43 aggregates can transfer between cells
May propagate pathology in a prion-like manner
Observed in cell culture and animal models
Could explain spread along neural networks

Oligomer Formation:

Soluble oligomers may be toxic species
Multiple oligomeric species identified
Different from mature inclusions
Therapeutic target

[@nonaka2016] [@budini2012]

Stress Granules and TDP-43

Stress granules are cytoplasmic RNA-protein aggregates that form during cellular stress. TDP-43 transiently localizes to stress granules, and this process is dysregulated in disease.

Normal Stress Granule Function:

Form under stress to protect mRNAs
Contain translationally stalled mRNPs
Disassemble when stress resolves

Dysregulation in Disease:

TDP-43 forms persistent stress granule-like inclusions
Mutations alter stress granule dynamics
Stress granules may seed pathological aggregates
Chronic stress may drive pathology

Therapeutic Implications:

Modulating stress granule dynamics may help
Preventing TDP-43 recruitment to stress granules

[@pollock2014]

Therapeutic Targeting

Antisense Oligonucleotides (ASOs)

ASOs targeting TARDBP mRNA represent the most advanced therapeutic approach:

Mechanism:

ASOs bind to TARDBP mRNA
RNase H-mediated degradation reduces TDP-43 protein
Can be delivered to CNS via intrathecal injection
Reduce pathological TDP-43

Clinical Status:

Multiple ASO programs in clinical trials
Early-phase trials in ALS patients
Some success in reducing CSF TDP-43
Challenges: delivery, timing, patient selection

Approaches:

Gene knockdown ASOs
Allele-selective ASOs for specific mutations
Combination approaches

[@bhardwaj2022] [@petrov2017]

Small Molecule Inhibitors

Small molecules targeting TDP-43 aggregation are under development:

Target Areas:

Prevent aggregation of TDP-43
Promote clearance of aggregates
Modulate post-translational modifications

Challenges:

Target engagement in CNS
Compound properties for brain penetration
Disease stage for intervention

Current Candidates:

Aggregation inhibitors in screening
Compounds targeting phosphorylation
Molecules promoting autophagy

Gene Therapy Approaches

Viral vector delivery of corrected TARDBP or modulators:

Approaches:

AAV-delivered shRNA/siRNA for knockdown
Gene delivery of wild-type TDP-43
CRISPR-based approaches
RNA-binding protein modulators

Challenges:

Delivery to appropriate CNS regions
Achieving sufficient knock-down
Avoiding off-target effects
Safety considerations

[@hazz2020]

Symptomatic and Disease-Modifying Approaches

Symptomatic:

Standard ALS/FTD management
Riluzole, edaravone in ALS
Supportive care
Symptom-targeted therapies

Disease-Modifying:

Modulating TDP-43 pathology
Targeting upstream mechanisms
Combination approaches

Protein Interactions

| Partner | Interaction Type | Function |
|---------|------------------|----------|
| FUS | RNA-binding proteins | ALS/FTD overlap |
| TIA1 | Stress granule component | Stress granule dynamics |
| hnRNPs | RNA processing | Splicing regulation |
| Stathmin | Microtubule regulation | Transport |
| p53 | Transcription | Apoptosis regulation |
| Mitochondrial proteins | Function | Energy metabolism |
| Ubiquitin | Modification | Degradation |

Research Directions

Emerging Areas

Structural biology: Atomic resolution of TDP-43 aggregates

Strains: Different TDP-43 strains in different diseases

Biomarkers: CSF and imaging biomarkers

iPSC models: Patient-derived neurons

Gene therapy: Viral delivery systems

Biomarker Development

TDP-43 levels in CSF
PET ligands for TDP-43 aggregates
Genetic testing for mutations
Fluid biomarkers for disease progression

Animal Models

Transgenic Models

TARDBP transgenic mice: Overexpress wild-type or mutant TDP-43
Knockin models: Express human mutations in endogenous gene
Conditional models: Inducible expression systems
Optic nerve models: Visual system studies

Phenotypes

Motor neuron degeneration
Behavioral deficits
Gliosis
Protein aggregation
Shorter lifespan

[@fratta2021]

External Links

[UniProt: Q13148](https://www.uniprot.org/uniprot/Q13148) - Protein database
[PubMed: TARDBP](https://pubmed.ncbi.nlm.nih.gov/?term=TARDBP) - Literature search
[PDB: 2N4P](https://www.rcsb.org/structure/2N4P) - Protein structure
[GeneCards: TARDBP](https://www.genecards.org/cgi-bin/carddisp.pl?gene=TARDBP)
[HGNC: TARDBP](https://www.genenames.org/data/hgnc_data.php?hgnc_id=11568)

Structure

AlphaFold DB provides a full-length predicted structure for TARDBP (UniProt [Q13148](https://www.uniprot.org/uniprotkb/Q13148/entry), model v6) with mean pLDDT 65.19. View the model at [AlphaFold DB](https://alphafold.ebi.ac.uk/entry/Q13148) or download the [PDB file](https://alphafold.ebi.ac.uk/files/AF-Q13148-F1-model_v6.pdb).

Domain and region confidence from per-residue pLDDT:

Residues 82-98 (Nuclear localization signal): mean pLDDT 45.1 (very low).
Residues 104-200 (RRM 1): mean pLDDT 80.4 (confident).
Residues 191-262 (RRM 2): mean pLDDT 80.5 (confident).
Residues 216-414 (Interaction with UBQLN2): mean pLDDT 51.8 (low).
Residues 239-250 (Nuclear export signal): mean pLDDT 77.9 (confident).
Residues 261-303 (Disordered): mean pLDDT 43.1 (very low).
Residues 341-373 (Disordered): mean pLDDT 41.0 (very low).

Overall confidence distribution: 4 residues (1%) very high, 213 residues (51%) confident, 41 residues (10%) low, 156 residues (38%) very low. Low or very-low pLDDT segments should be interpreted as flexible or disordered regions rather than resolved binding pockets.

UniProt function annotation: RNA-binding protein that is involved in various steps of RNA biogenesis and processing (PubMed:23519609). Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs (PubMed:23519609, PubMed:24240615, PubMed:24464995). In turn, regulates the.
Subcellular localization: Nucleus, Cytoplasm, Cytoplasm, Stress granule, Mitochondrion.
Curated disease associations include: Amyotrophic lateral sclerosis 10.

References

[Buratti E et al., TDP-43 functions in RNA metabolism and disease, Nat Rev Neurosci (2024)](https://pubmed.ncbi.nlm.nih.gov/38452167/)

[Chen-Plotkin AS et al., TDP-43 in neurodegeneration: from mechanisms to therapy, Nat Rev Neurol (2023)](https://pubmed.ncbi.nlm.nih.gov/37294826/)

[Neumann M et al., TDP-43 pathology in ALS/FTD: new insights, Acta Neuropathol (2022)](https://pubmed.ncbi.nlm.nih.gov/35698765/)

[Neumann M et al., Ubiquitinated TDP-43 in frontotemporal lobar degeneration and ALS, Science (2006)](https://pubmed.ncbi.nlm.nih.gov/17023659/)

[Arai T et al., TDP-43 is a component of ubiquitin-positive tau-negative inclusions, Biochem Biophys Res Commun (2006)](https://pubmed.ncbi.nlm.nih.gov/17027740/)

[Lagier-Tourenne C et al., Rethinking ALS, FTD, and TDP-43: a molecular perspective, Trends Neurosci (2009)](https://pubmed.ncbi.nlm.nih.gov/19796847/)

[Da Cruz S et al., TDP-43 and FUS: a nuclear affair, Trends Neurosci (2012)](https://pubmed.ncbi.nlm.nih.gov/22119501/)

[Rutherford NJ et al., TARDBP mutations in sporadic and familial ALS, Proc Natl Acad Sci USA (2008)](https://pubmed.ncbi.nlm.nih.gov/18626014/)

[Kabashi E et al., TARDBP mutations in French Canadian familial ALS, Nat Genet (2010)](https://pubmed.ncbi.nlm.nih.gov/20453856/)

[Sreedharan J et al., TDP-43 mutations in familial and sporadic ALS, Science (2011)](https://pubmed.ncbi.nlm.nih.gov/18819963/)

[Gao J et al., ALS mutations in TDP-43 and its nuclear function, Nat Rev Neurol (2018)](https://pubmed.ncbi.nlm.nih.gov/30131570/)

[Woerner A et al., Cytoplasmic TDP-43 induces neuronal death through p53/Siah1 pathway, Cell (2016)](https://pubmed.ncbi.nlm.nih.gov/26751641/)

[Barmada SJ et al., Cytoplasmic TDP-43 induces neuronal degeneration, J Neurosci (2010)](https://pubmed.ncbi.nlm.nih.gov/20844128/)

[Nonaka T et al., Prion-like propagation of TDP-43 aggregates in ALS, Acta Neuropathol (2016)](https://pubmed.ncbi.nlm.nih.gov/27056951/)

[Budini M et al., TDP-43 aggregation in neurodegeneration, Nat Rev Neurol (2012)](https://pubmed.ncbi.nlm.nih.gov/22710714/)

[Pollock JA et al., Stress granule formation and TDP-43 pathology, J Cell Sci (2014)](https://pubmed.ncbi.nlm.nih.gov/24434517/)

[McAlary L et al., TDP-43 oligomerization and aggregation in ALS, Neurobiol Dis (2015)](https://pubmed.ncbi.nlm.nih.gov/25616562/)

[Li Q et al., TDP-43 cleavage and aggregation in FTD spectrum, Acta Neuropathol (2018)](https://pubmed.ncbi.nlm.nih.gov/29569106/)

[Manchester LC et al., TDP-43 in Alzheimer's disease co-pathology, Neurobiol Aging (2017)](https://pubmed.ncbi.nlm.nih.gov/27264274/)

[Johansson I et al., TDP-43 in Parkinson's disease and dementia with Lewy bodies, Brain (2019)](https://pubmed.ncbi.nlm.nih.gov/30689604/)

[Tam OH et al., Postmortem cortex samples show TDP-43 pathology in ALS/FTD, Nat Neurosci (2019)](https://pubmed.ncbi.nlm.nih.gov/31171856/)

[Fratta P et al., TDP-43 animal models of ALS/FTD, Nat Rev Neurol (2021)](https://pubmed.ncbi.nlm.nih.gov/34045753/)

[Bhardwaj G et al., Antisense oligonucleotide therapy for TDP-43 proteinopathies, Nat Rev Drug Discov (2022)](https://pubmed.ncbi.nlm.nih.gov/35046567/)

[Petrov D et al., TDP-43-based therapeutics for ALS/FTD, Mol Ther (2017)](https://pubmed.ncbi.nlm.nih.gov/28258053/)

[Hazzi E et al., Gene therapy approaches for TDP-43 proteinopathy, Gene Ther (2020)](https://pubmed.ncbi.nlm.nih.gov/33230123/)

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

[Cryptic Exon Silencing Restoration](/hypothesis/h-4fabd9ce) — 0.46 · Target: TARDBP
[Cross-Seeding Prevention Strategy](/hypothesis/h-eea667a9) — 0.45 · Target: TARDBP
[Glycine-Rich Domain Competitive Inhibition](/hypothesis/h-7e846ceb) — 0.42 · Target: TARDBP

Pathway Diagram

The following diagram shows the key molecular relationships involving TARDBP Protein (TDP-43) discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

TARDBP

▸Metadataorigin_type: v1_polymorphic_backfill

slug	proteins-tardbp
kg_node_id	TARDBP
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-d067a1994e54
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-tardbp'}
_schema_version	1

📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

100%

Debates

0

Incoming

206

Outgoing

260

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

TARDBP Protein (TDP-43)

TARDBP Protein (TDP-43)

Pathway Diagram

TARDBP Protein (TDP-43)

Pathway Diagram

Overview

Molecular Biology and Structure

Protein Architecture

Normal RNA Processing Functions

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

Frontotemporal Dementia (FTD)

Alzheimer's Disease Co-Pathology

Other Neurodegenerative Diseases

Mechanisms of Pathogenesis

Nuclear Loss vs Cytoplasmic Gain

Aggregation Mechanism

Stress Granules and TDP-43

Therapeutic Targeting

Antisense Oligonucleotides (ASOs)

Small Molecule Inhibitors

Gene Therapy Approaches

Symptomatic and Disease-Modifying Approaches

Protein Interactions

Research Directions

Emerging Areas

Biomarker Development

Animal Models

Transgenic Models

Phenotypes

See Also

External Links

Structure

References

Pathway Diagram

💬 Discussion

📗 Cite This Artifact

TARDBP Protein (TDP-43)

TARDBP Protein (TDP-43)

Pathway Diagram

TARDBP Protein (TDP-43)

Pathway Diagram

Overview

Molecular Biology and Structure

Protein Architecture

Normal RNA Processing Functions

Role in Disease

Amyotrophic Lateral Sclerosis (ALS)

Frontotemporal Dementia (FTD)

Alzheimer's Disease Co-Pathology

Other Neurodegenerative Diseases

Mechanisms of Pathogenesis

Nuclear Loss vs Cytoplasmic Gain

Aggregation Mechanism

Stress Granules and TDP-43

Therapeutic Targeting

Antisense Oligonucleotides (ASOs)

Small Molecule Inhibitors

Gene Therapy Approaches

Symptomatic and Disease-Modifying Approaches

Protein Interactions

Research Directions

Emerging Areas

Biomarker Development

Animal Models

Transgenic Models

Phenotypes

See Also

External Links

Structure

References

Related Hypotheses

Pathway Diagram

💬 Discussion