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.

2220Connections

1Hypotheses

1Analyses

50Outgoing

50Incoming

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	ALS, ATP, Aging, Alzheimer, Alzheimer'S Disease
Known Drugs/Compounds	IRN, Gastrodin, hesperetin, DHT, FREE HEME, IRINOTECAN
Interactions	SNCA, CD68, MMP2, EGFR, GSDMD, MYD88
SciDEX Target	View Target Profile (4 clinical trials)
SciDEX Hypotheses	Selective TLR4 Modulation to Prevent Gut-Derived N
KG Connections	2220 knowledge graph edges
Databases	GeneCards HPA STRING

🧬 3D Structure: TLR4 — PDB 3FXI Click to expand

Experimental structure from RCSB PDB | Powered by Mol*

Wiki Pages (21)

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 (1300)

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

Incoming (920)

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
TNF	associated_with	gene	0.90
CIRP	binds_to	protein	0.90
CASP3	associated_with	gene	0.90
DHT	inhibits	drug	0.90
NLRP3	co_mentioned_with	gene	0.90
NEURODEGENERATION	associated_with	gene	0.90
AMYLOID	associated_with	protein	0.90
h-2e7eb2ea	targets_gene	hypothesis	0.90
h-f3fb3b91	targets_gene	hypothesis	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
MICROGLIA	associated_with	gene	0.82
APOPTOSIS	associated_with	gene	0.82
PARKINSON'S DISEASE	associated_with	disease	0.82
h-2e7eb2ea	targets	hypothesis	0.80
ADK	upstream_of	protein	0.80
IL1B	co_mentioned_with	gene	0.80
CASTRATION	upregulates	biological_process	0.80
SEMAGLUTIDE	inhibits	drug	0.80
ABETA	activates	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
STAT3	activates	gene	0.70
NLRP3	activates	gene	0.70
IL6	activates	gene	0.70
Gastrodin	inhibits	drug	0.70
BECN1	activates	gene	0.70
hesperetin	inhibits	drug	0.70
UBIQUITIN	activates	gene	0.70
TNF	regulates	gene	0.70
PI3K	activates	gene	0.70
TH	regulates	gene	0.70
LPS	activates	drug	0.70
ERK	inhibits	gene	0.70
PHAGOCYTOSIS	activates	gene	0.70
C-JUN	activates	gene	0.70
NEURODEGENERATION	implicated_in	gene	0.70
INFLAMMATION	activates	gene	0.70
ROS	activates	gene	0.70

Targeting Hypotheses (1)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Selective TLR4 Modulation to Prevent Gut-Derived Neuroinflam	0.617	neurodegeneration	What are the mechanisms by which gut mic

Mentioning Analyses (1)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-01 | 20 hypotheses Top: 0.617

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
Panax ginseng-derived Exosome-like Nanoparticles Prevent LPS-induced Septic Shoc [PMID:41530048]	Kim Y, Kim YK, Lee S, Kim M, Lee SW et a	Mol Pharm	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
Reverse vaccinology and immunoinformatics Approaches Driven designing of a Novel [PMID:41934706]	Siddiquee NH, Al Mamun MA, Dremit TI, Ul	Hum Immunol	2026	0
MEX3B aggravates osteoarthritis progression by post-transcriptionally activating [PMID:41935341]	Fu Z, Huang Y, Zhang S, Chen J	J Orthop Surg Res	2026	0
Hierarchical Targeting of TREM2(+) Myeloid Cells via Acid-Triggered OMVs Reprogr [PMID:41945876]	Chen F, Xue Y, Ma X, Chen L, Shao Z et a	Adv Sci (Weinh)	2026	0
Molecular characterization and immunoinformatics-based design of a multi-epitope [PMID:41949632]	Asim M, Makki HH	Antonie Van Leeuwenhoek	2026	0
Zearalenone causes female reproductive lipotoxicity through the ERα-CD36/TLR4 si [PMID:41957128]	Dai C, Fu W, Huang Y, Li T, Ma Z et al.	Commun Biol	2026	0
Protective effect of nebivolol on bleomycin-induced lung fibrosis via suppressin [PMID:41960705]	Morsy MA, Abdel-Gaber SA, Abed El Baky M	Immunopharmacol Immunotoxicol	2026	0
Astrocytic calcium-dependent enzyme PAD2 governs microglia activity to exacerbat [PMID:41962542]	Zhang J, Huang Y, Chen Y, Zhang Y, Chen	Immunity	2026	0
Inhibition of TLR4/TRAF6/NF-κB pathway by empagliflozin mitigates concanavalin A [PMID:41964671]	El-Kashef DH, Shawky NO, Mahdi L, Sewila	Naunyn Schmiedebergs Arch Phar	2026	0

TLR4

Understanding Entity Pages

Summary

Wiki Pages (21)

TLR4 (Redirect)

Corticobasal Syndrome (CBS)

Atypical Parkinsonism

Device Therapies Comparison for CBS/PSP

Therapeutics

neuroinflammation

Neuroimmune Response in 4R-Tauopathies: Cross-Disease Comparison

Synucleinopathy Mechanism

Spinal Cord Dorsal Horn Neurons

Alpha-Synuclein Prion-Like Spreading Mechanisms in Parkinson's Disease

Synucleinopathies

Gut-Brain Axis in Neurodegeneration

NF-kB Signaling Pathway in Neurodegeneration

Pannexin 1 and P2X7 Receptor Signaling in Neurodegeneration

NF-κB Signaling Pathway in Neurodegeneration

Necroptotic Neurons

Neuroinflammation Across AD, PD, ALS, FTD, and HD

Gut-Microbiome-Neurodegeneration Axis

Alpha-Synuclein Aggregation Pathway

Neuroinflammation in Parkinson's Disease