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.

2306Connections

2Hypotheses

2Analyses

50Outgoing

50Incoming

5Experiments

2Debates

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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🧬 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, Ezetimibe, FREE HEME, Gastrodin, hesperetin
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	2306 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 (1269)

Target	Relation	Type	Str
Als	therapeutic_target	disease	1.00
Toll-Like Receptor	activates	pathway	1.00
TNF-Α	activates	gene	1.00
Neuroinflammation	activates	disease	1.00
Inflammation	activates	disease	1.00
Alzheimer	activates	disease	1.00
MICROGLIA	activates	gene	1.00
NEUROINFLAMMATION	activates	gene	1.00
INFLAMMATION	activates	gene	1.00
NF-ΚB	activates	gene	1.00
UBIQUITIN	activates	gene	1.00
Nf-Κb	regulates	pathway	1.00
Inflammation	inhibits	disease	1.00
INFLAMMATION	inhibits	gene	1.00
NF-ΚB	inhibits	gene	1.00
autophagy	activates	process	1.00
Autophagy	activates	pathway	1.00
Nf-Κb	activates	pathway	1.00
Als	activates	disease	1.00
TNF-Α	inhibits	gene	1.00
Nf-Κb	inhibits	pathway	1.00
Tumor	inhibits	disease	1.00
Toll-Like Receptor	inhibits	pathway	1.00
Oxidative Stress	therapeutic_target	pathway	1.00
ALZHEIMER	activates	gene	1.00
TRAF6	activates	protein	1.00
Oxidative Stress	activates	pathway	1.00
Immune Response	activates	pathway	1.00
NF-ΚB	regulates	gene	1.00
Neurodegeneration	activates	disease	0.95
Parkinson	activates	disease	0.95
Tumor	activates	disease	0.95
Neuroinflammation	inhibits	disease	0.95
microglia	activates	cell_type	0.90
IL-1Β	upregulates	protein	0.90
NF-kB	activates	pathway	0.90
TNF-Α	upregulates	protein	0.90
ERK/p38 signaling	activates	pathway	0.90
NF-κB	associated_with	pathway	0.90
microglia	expressed_in	cell_type	0.90
NF-kB signaling	participates_in	pathway	0.90
PI3K	inhibits	gene	0.90
APP	activates	gene	0.90
MYD88	activates	gene	0.90
OXIDATIVE STRESS	therapeutic_target	gene	0.90
IL-6	activates	gene	0.90
IL-6	inhibits	gene	0.90
Toll-Like Receptor	associated_with	pathway	0.90
Mapk	activates	pathway	0.90
GENES	activates	gene	0.90

Incoming (1037)

Source	Relation	Type	Str
NF-KB	associated_with	protein	1.00
ALZHEIMER'S DISEASE	associated_with	disease	1.00
IL-6	associated_with	gene	0.98
Cyclosporine A	downregulates	drug	0.92
CIRP	binds_to	protein	0.90
AMYLOID	associated_with	protein	0.90
h-2e7eb2ea	targets	hypothesis	0.90
TNF	associated_with	gene	0.90
CASP3	associated_with	gene	0.90
NEURODEGENERATION	associated_with	gene	0.90
NLRP3	associated_with	gene	0.90
h-f3fb3b91	targets	hypothesis	0.90
DHT	inhibits	drug	0.90
NEURODEGENERATION	activates	gene	0.90
FREE HEME	activates	drug	0.88
CEREBROLYSIN	downregulates	drug	0.87
OREXIN-A	inhibits	protein	0.85
ADK	regulates	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
PARKINSON'S DISEASE	associated_with	disease	0.82
MICROGLIA	associated_with	gene	0.82
IL1B	associated_with	gene	0.80
ADK	upstream_of	protein	0.80
SEMAGLUTIDE	inhibits	drug	0.80
ABETA	activates	protein	0.80
CASTRATION	upregulates	biological_process	0.80
NLRP3	inhibits	gene	0.80
TNF	inhibits	gene	0.74
IRN	inhibits	drug	0.72
IL-1B	associated_with	gene	0.72
IBA1	activates	gene	0.70
APP	inhibits	gene	0.70
NLRP3	expressed_in	gene	0.70
GFAP	biomarker_for	gene	0.70
GASDERMIN	expresses	gene	0.70
NLRP3	biomarker_for	gene	0.70
LRP1	activates	gene	0.70
CGAS	enhances	gene	0.70
MLKL	activates	gene	0.70
ENDOTHELIAL	activates	cell_type	0.70
MACROPHAGE	expresses	cell_type	0.70
NRF2	targets	gene	0.70
CYP46A1	activates	gene	0.70
STAT3	expresses	gene	0.70
INSULIN SIGNALING	activates	pathway	0.70
NEURONS	associated_with	cell_type	0.70
SIRT1	targets	gene	0.70
STING	causes	gene	0.70

Targeting Hypotheses (2)

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

Mentioning Analyses (2)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-01 | 5 hypotheses Top: 0.720

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

neurodegeneration | 2026-04-01 | 13 hypotheses Top: 0.888

Experiments (5)

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

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 (2)

Multi-agent debates referencing this entity

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

closed · Rounds: 4 · Score: 0.82 · 2026-04-22

What are the mechanisms underlying what are the mechanisms by which gut microbio

closed · Rounds: 4 · Score: 0.95 · 2026-04-01

Related Research

Hypotheses and analyses mentioning TLR4 in their description or question text

No additional research found

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 (1269)

Incoming (1037)

Targeting Hypotheses (2)

Mentioning Analyses (2)

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 (5)

Related Papers (20)

Debates (2)

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

What are the mechanisms underlying what are the mechanisms by which gut microbio

Related Research