gene

TLR4

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about TLR4: 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.

2314Connections

6Hypotheses

9Analyses

50Outgoing

50Incoming

7Experiments

14Debates

Summary

TLR4 is a gene implicated in neurodegeneration research. Key relationships include: activates, inhibits, regulates. Associated with ALS, ALZHEIMER'S DISEASE, Aging. Connected to 943 entities in the SciDEX knowledge graph.

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AI-generated illustration · click image to enlarge

Regenerate portrait ↻

🧬 Gene Info

Gene Symbol	TLR4
Full Name	Toll-Like Receptor 4
Chromosome	9q33.1
Protein Type	Receptor
Target Class	Receptor
Function	LBP transfer: LPS-binding protein transfers LPS to CD14
Mechanism of Action	Small molecule antagonist or antibody blocking TLR4-mediated neuroinflammatory signaling
Druggability	Low (0.41)
Clinical Stage	Phase III
Molecular Weight	95 kDa
Pathways	Akt, Amyloid, Apoptosis, Autophagy, Cell Division
UniProt ID	O00206
NCBI Gene ID	7099
Ensembl ID	ENSG00000136869
OMIM	603030
GeneCards	TLR4
Human Protein Atlas	TLR4
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	DHT, DOXORUBICIN, Eritoran, Ezetimibe, FREE HEME, Gastrodin
Interactions	ABETA, ACAT1, Actin, AD, AGING, AHR
SciDEX Target	View Target Profile (4 clinical trials)
SciDEX Hypotheses	Selective TLR4 Modulation to Prevent Gut-Derived N
KG Connections	2313 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure Comparison — TLR4 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

3FXI — X-ray / Cryo-EM

🔮 AI Predicted Structure

O00206 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (5)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

flowchart TD
    TLR4(["TLR4"])
    Nf__b["Nf-Kappab"]
    Als["Als"]
    Inflammation["Inflammation"]
    Neuroinflammation["Neuroinflammation"]
    Toll_Like_Receptor["Toll-Like Receptor"]
    Autophagy["Autophagy"]
    Tumor["Tumor"]
    Alzheimer["Alzheimer"]
    TNF__(["TNF-Alpha"])
    UBIQUITIN(["UBIQUITIN"])
    INFLAMMATION(["INFLAMMATION"])

    TLR4 -->|"activates"| Nf__b
    TLR4 -->|"activates"| Als
    TLR4 -->|"activates"| Inflammation
    TLR4 -->|"activates"| Neuroinflammation
    TLR4 -->|"activates"| Toll_Like_Receptor
    TLR4 -.->|"inhibits"| Inflammation
    TLR4 -->|"therapeutic target"| Als
    TLR4 -->|"regulates"| Nf__b
    TLR4 -->|"activates"| Autophagy
    TLR4 -.->|"inhibits"| Tumor
    TLR4 -.->|"inhibits"| Nf__b
    TLR4 -->|"activates"| Alzheimer
    TLR4 -.->|"inhibits"| TNF__
    TLR4 -->|"activates"| UBIQUITIN
    TLR4 -.->|"inhibits"| INFLAMMATION

    style TLR4 fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (1278)

Target	Relation	Type	Str
TLR4	encodes	protein	0.00
INFLAMMATION	activates	gene	1.00
UBIQUITIN	activates	gene	1.00
Toll-Like Receptor	activates	pathway	1.00
INFLAMMATION	inhibits	gene	1.00
TNF-Α	activates	gene	1.00
MICROGLIA	activates	gene	1.00
Autophagy	activates	pathway	1.00
Als	activates	disease	1.00
NF-ΚB	inhibits	gene	1.00
Als	therapeutic_target	disease	1.00
Inflammation	inhibits	disease	1.00
Inflammation	activates	disease	1.00
Nf-Κb	activates	pathway	1.00
autophagy	activates	process	1.00
Neuroinflammation	activates	disease	1.00
TNF-Α	inhibits	gene	1.00
Alzheimer	activates	disease	1.00
Nf-Κb	inhibits	pathway	1.00
Tumor	inhibits	disease	1.00
NF-ΚB	activates	gene	1.00
NEUROINFLAMMATION	activates	gene	1.00
Nf-Κb	regulates	pathway	1.00
Oxidative Stress	therapeutic_target	pathway	1.00
Immune Response	activates	pathway	1.00
NF-ΚB	regulates	gene	1.00
Oxidative Stress	activates	pathway	1.00
TRAF6	activates	protein	1.00
ALZHEIMER	activates	gene	1.00
Toll-Like Receptor	inhibits	pathway	1.00
Parkinson	activates	disease	0.95
Neuroinflammation	inhibits	disease	0.95
Tumor	activates	disease	0.95
Neurodegeneration	activates	disease	0.95
NF-kB activation	activates	pathway	0.90
microglia	activates	cell_type	0.90
microglia	expressed_in	cell_type	0.90
NF-kB	activates	pathway	0.90
NF-kB signaling	participates_in	pathway	0.90
NF-κB	associated_with	pathway	0.90
NF-κB signaling	activates	pathway	0.90
ERK/p38 signaling	activates	pathway	0.90
systemic_inflammation	activates	mechanism	0.90
TNF-Α	upregulates	protein	0.90
IL-1Β	upregulates	protein	0.90
Apoptosis	activates	pathway	0.90
IL-6	inhibits	gene	0.90
Invasion	activates	pathway	0.90
TNF	activates	gene	0.90
GENES	activates	gene	0.90

Incoming (1036)

Source	Relation	Type	Str
TLR4	encodes	gene	0.00
ALZHEIMER'S DISEASE	associated_with	disease	1.00
NF-KB	associated_with	protein	1.00
IL-6	associated_with	gene	0.98
Cyclosporine A	downregulates	drug	0.92
h-2e7eb2ea	targets	hypothesis	0.90
NLRP3	associated_with	gene	0.90
AMYLOID	associated_with	protein	0.90
h-f3fb3b91	targets	hypothesis	0.90
DHT	inhibits	drug	0.90
NEURODEGENERATION	associated_with	gene	0.90
CIRP	binds_to	protein	0.90
TAK-242	inhibits	drug	0.90
Eritoran	inhibits	drug	0.90
TNF	associated_with	gene	0.90
CASP3	associated_with	gene	0.90
NEURODEGENERATION	activates	gene	0.90
FREE HEME	activates	drug	0.88
CEREBROLYSIN	downregulates	drug	0.87
ADK	regulates	protein	0.85
OREXIN-A	inhibits	protein	0.85
SDA-2026-04-01-gap-20260401-225155	targets	analysis	0.85
LGALS3	interacts_with	protein	0.84
APOPTOSIS	associated_with	gene	0.82
MICROGLIA	associated_with	gene	0.82
PARKINSON'S DISEASE	associated_with	disease	0.82
IL1B	associated_with	gene	0.80
ABETA	activates	protein	0.80
SEMAGLUTIDE	inhibits	drug	0.80
CASTRATION	upregulates	process	0.80
ADK	upstream_of	protein	0.80
NLRP3	inhibits	gene	0.80
TNF	inhibits	gene	0.74
IRN	inhibits	drug	0.72
IL-1B	associated_with	gene	0.72
GFAP	expressed_in	gene	0.70
NLRP3	expressed_in	gene	0.70
NLRP3	biomarker_for	gene	0.70
NRF2	targets	gene	0.70
STAT3	expresses	gene	0.70
TAU	activates	gene	0.70
SIRT1	targets	gene	0.70
MACROPHAGE	activates	cell_type	0.70
APP	inhibits	gene	0.70
GFAP	biomarker_for	gene	0.70
ENDOTHELIAL	activates	cell_type	0.70
NEURONS	associated_with	cell_type	0.70
STING	enhances	gene	0.70
NEURONS	activates	cell_type	0.70
GASDERMIN	expresses	gene	0.70

Targeting Hypotheses (6)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflam	0.789	neurodegeneration	What are the mechanisms by which gut mic
TLR4/MyD88/NF-κB Axis Blockade to Interrupt LPS-Mediated Gut	0.703	neurodegeneration	How do gut microbiome-derived metabolite
Leaky Gut LPS Translocation Activates Systemic TLR4/MyD88 Si	0.670	neurodegeneration	How does gut microbiome dysbiosis contri
LPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target	0.619	neurodegeneration	Gut-Brain Axis in Parkinson's Disease: M
H2S/butyrate imbalance drives enteric alpha-synuclein pathol	0.380	Parkinson's disease	-

TLR4 priming is the actionable driver in: How does gut micro	0.343	neurodegeneration	How does gut microbiome dysbiosis contri

Mentioning Analyses (9)

Scientific analyses that reference this entity

Experiments (7)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Resveratrol protection against renal I/R injury in diabetic rats	validation	diabetic nephropathy	0.900	streptozotocin-induced diabeti	proposed	N/A
TLR4 Activation Assay with NETs and Anti-CarP Antibodies	exploratory	rheumatoid arthritis	0.850	HEK293 TLR4 reporter cells	proposed	N/A
TLR expression analysis in Parkinson's disease patients	clinical	Parkinson's disease	0.850	human patients	proposed	N/A
Resveratrol effects on HK-2 cells under hypoxia/reoxygenation	exploratory	diabetic nephropathy	0.850	HK-2 cells cultured in high gl	proposed	N/A
TLR expression in α-synuclein overexpressing mice	validation	Parkinson's disease	0.800	mice overexpressing human α-sy	proposed	N/A
Single nucleus RNA-seq and ATAC-seq of postmortem PD brain tissue (n=1	gene_expression	Parkinson's disease	0.500	postmortem_human_tissue	extracted	N/A
Individuals with SNCA pathogenic variants reported painful dystonia, l	genetic_association	Parkinson's disease	0.500	human	extracted	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Ca [PMID:35642214]	Wang M, Pan W, Xu Y, Zhang J, Wan J, Jia	J Inflamm Res	2022	1
Podocyte TLR4 deletion alleviates diabetic kidney disease through prohibiting PK [PMID:40659086]	Li Z, Tan D, Lin J, Zhang T, Liu B et al	J Adv Res	2026	0
Celastrol treatment attenuates the inflammatory response in Alzheimer's disease [PMID:40762111]	Cao F, Zhang P, Zheng Z, Wang P, Wang Y	Neurol Res	2026	0
CircCramp1l targets the miR-532-3p/HMGB1/Drp1 axis to regulate allergic rhinitis [PMID:41519399]	Zhang Y, Wang J, Song Y, Chai J, Li L et	Biochem Pharmacol	2026	0
Neuronal TLR4 upregulation activates the cGAS-STING pathway to induce ferroptosi [PMID:41702081]	Qin H, Yang L, Du J, Xu X, Chen Z et al.	Int Immunopharmacol	2026	0
2'-Fucosyllactose Alleviates Metabolic Hypertension in Mice via Gut Microbiota M [PMID:41926238]	Chen J, Liang S, Liu D, Yang S, Yan Q et	J Agric Food Chem	2026	0
Leveraging intraperitoneal delivery of toll-like receptor agonists to treat peri [PMID:41926324]	Yan H, Chia D, Ernst S, Demuytere J, Cos	Expert Opin Drug Deliv	2026	0
Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses [PMID:41927877]	Miao J, Wang J, Zhou W, Guo J	Sci Rep	2026	0
Anti-carbamylated protein antibodies stabilize carbamylated Histone H3 to promot [PMID:41930627]	Nakabo S, Hanata N, Patino-Martinez E, H	Arthritis Rheumatol	2026	0
In silico design of a novel multi-epitope mRNA vaccine candidate for BtHKU5-CoV- [PMID:41931545]	Zheng N, Xu Y	PLoS Negl Trop Dis	2026	0
Upstream ORFs control TNFR1 abundance and tissue tolerance to TNF. [PMID:41931597]	Ma B, Lyu W, Rizk J, Han X, Kjær M et al	Sci Immunol	2026	0
Interweaving microglial senescence and gut microbiome dynamics in Alzheimer's di [PMID:41747877]	Waghmare A, Rahangdale S, Khare K, Taksa	Molecular and cellular neurosc	2026	0
Nanopiezoelectric 3D-Bioprinted Neural Organoid Models Epileptic Neuron-Microgli [PMID:41877549]	Chu J, Hu K, Lee WF, Xu SJ, Sun Z, Xu Y,	Nano letters	2026	0
The Neuroameliorative Effects of Enzymatically Modified Isoquercitrin and Sodium [PMID:41880086]	Hassouna I, Hassanein OH, El-Elaimy IA,	Neurochemical research	2026	0
Role of Pentacyclic Triterpenes in the Management of Neurological Disorders: An [PMID:41870813]	Upadhayay S	Molecular neurobiology	2026	0
Hyperglycaemia-induced metabolic stress and epigenetic imprinting in the inflamm [PMID:41730508]	Razi FB, Ashraf H, Singhal S, Qamar Z, M	Diabetes research and clinical	2026	0
Colonic Barrier Dysfunction and Inflammation Induced by Nano-/Micro-Plastics Fib [PMID:41923296]	Li Y, Bao S, Huang P, Wang J, Li H, Liu	Journal of applied toxicology	2026	0
Artemisinin attenuates 3-nitropropionic acid-induced neurodegeneration via HMGB1 [PMID:41865324]	Mustafa AM, Mudhafar M, Elgindy AM, Esma	Archives of pharmacal research	2026	0
Curcumin and Glycyrrhiza glabra Synergistically Attenuate Alzheimer's Pathology [PMID:41920384]	Liu S, Yan J, Dong J	Neurochemical research	2026	0
The spleen-brain axis in Alzheimer's disease and related dementias: Integrating [PMID:41778859]	Yan J, Zhang J, Ye X, Wang H, Li H, Li W	Alzheimer's & dementia : the j	2026	0

Debates (14)

Multi-agent debates referencing this entity

Related Research

Hypotheses and analyses mentioning TLR4 in their description or question text

TLR4 priming is the actionable driver in: How does gut microbiome dysbiosis cont

Score: 0.343 · neurodegeneration · 2026-04-26

The gap can be tested by treating TLR4 priming as an upstream driver rather than a passive correlate. If true, perturbin

TLR4

Understanding Entity Pages

Summary

Wiki Pages (5)

Toll-Like Receptor 4 (TLR4)

TLR4 Antagonists for Neurodegeneration

TLR4 Gene

TLR4 Protein

TLR4 (Redirect)

Pathway Diagram

Outgoing (1278)

Incoming (1036)

Targeting Hypotheses (6)

Mentioning Analyses (9)

Gut-Brain Axis in Parkinson's Disease: Molecular Mechanisms, Neuroinflammation,

How do gut microbiome-derived metabolites SCFAs LPS TMAO influence alpha-synucle

What determines the GPX4/ACSL4 balance that switches microglia from protective t

How does engineered C. butyricum cross the blood-brain barrier to directly bind

How can senescent microglia be molecularly distinguished from beneficial activat

Neuroinflammation and microglial priming in early Alzheimer's Disease

Gut-Brain Axis Therapeutics for Alzheimer's Disease

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (7)

Related Papers (20)

Debates (14)

Hypothesis debate: SCFA Deficiency Disrupts Microglial Homeostasis and Promotes

Hypothesis debate: Vagus Nerve as Anatomical Highway for Prion-Like α-Syn Propag

Hypothesis debate: Enteric Nervous System Dysfunction as Self-Reinforcing Pathol

Hypothesis debate: LPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target

What are the key molecular mechanisms by which gut microbiome dysbiosis drives n

This analysis aims to elucidate the mechanisms by which gut microbiome dysbiosis

The debate revealed that microglial senescence markers are poorly defined compar

How do gut microbiome-derived metabolites SCFAs LPS TMAO influence alpha-synucle

While ACSL4-driven ferroptosis was strongly supported, the molecular triggers th

The abstract claims C. butyricum-GLP-1 crosses the BBB and binds to GLP-1 recept

Related Research

TLR4 priming is the actionable driver in: How does gut microbiome dysbiosis cont