gene

NLR

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NLR: 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.

1126Connections

30Hypotheses

1Analyses

50Outgoing

50Incoming

4Experiments

1Debates

Summary

Page for NLR Family Member X1

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🧬 Gene Info

Gene Symbol	NLR
Primary Expression	substantia nigra, Substantia Nigra
Amino Acids	977 aa
Pathways	NF-κB
GeneCards	NLR
Human Protein Atlas	NLR
Associated Diseases	Als, Alzheimer, Cancer, Cardiovascular, dementia
Known Drugs/Compounds	dimethyl fumarate, rapamycin
Interactions	ABCD3, ABP, ACTB, Actin, AGING, AIF1
KG Connections	1126 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (20)

Knowledge base pages for this entity

Validated Hypothesis: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration

hypothesis · 5476 words

→

Validated Hypothesis: Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous Neurodegeneration

hypothesis · 5442 words

→

Pathway Diagram

graph TD
    NLR["NLR"]
    Alzheimer["Alzheimer"]
    Cardiovascular["Cardiovascular"]
    Parkinson["Parkinson"]
    Dementia["Dementia"]
    Frontotemporal_Dementia["Frontotemporal Dementia"]
    Cancer["Cancer"]
    Fibrosis["Fibrosis"]
    Neurodegeneration["Neurodegeneration"]
    Aging["Aging"]
    Tumor["Tumor"]
    ALS["ALS"]
    Inflammation["Inflammation"]
    Neuroinflammation["Neuroinflammation"]
    NLR <-->|"interacts"| Alzheimer
    NLR <-->|"interacts"| Cardiovascular
    NLR <-->|"interacts"| Parkinson
    NLR <-->|"interacts"| Dementia
    NLR <-->|"interacts"| Frontotemporal_Dementia
    NLR <-->|"interacts"| Cancer
    NLR <-->|"interacts"| Fibrosis
    NLR -.->|"inhibits"| Neurodegeneration
    NLR -.->|"inhibits"| Parkinson
    NLR -.->|"inhibits"| Aging
    NLR -->|"regulates"| Tumor
    NLR -.->|"inhibits"| ALS
    NLR -.->|"inhibits"| Inflammation
    NLR -.-|"associated"| Tumor
    NLR -->|"activates"| Inflammation
    NLR -->|"activates"| Neurodegeneration
    NLR -->|"activates"| Neuroinflammation
    NLR -->|"activates"| Parkinson
    NLR -->|"activates"| Tumor
    NLR -->|"activates"| ALS
    style NLR fill:#006494,stroke:#333,color:#e0e0e0,stroke-width:2px

Outgoing (608)

Target	Relation	Type	Str
pyroptosis	participates_in	pathway	0.90
autophagy pathway	participates_in	pathway	0.90
oxidative stress response	participates_in	pathway	0.90
necroptosis	participates_in	pathway	0.80
OPTN	regulates	gene	0.80
MAPK signaling	participates_in	pathway	0.80
ROS	activates	gene	0.80
neural stem cells	activates	cell_type	0.80
ubiquitin-proteasome	participates_in	pathway	0.80
microglia	activates	cell_type	0.80
SQSTM1	activates	gene	0.80
neural stem cells	regulates	cell_type	0.80
ROS	regulates	gene	0.80
JAK-STAT signaling	participates_in	pathway	0.70
dendritic cells	activates	cell_type	0.70
RB1CC1	regulates	gene	0.70
OPTN	activates	gene	0.70
NLRP3	causes	gene	0.70
STAT3	regulates	gene	0.70
RB1	regulates	gene	0.70
RIPK3	regulates	gene	0.70
PINK1	regulates	gene	0.70
PI3K	regulates	gene	0.70
dendritic cells	regulates	cell_type	0.70
PTEN	regulates	gene	0.70
unfolded protein response	participates_in	pathway	0.70
RB1CC1	activates	gene	0.70
RB1	activates	gene	0.70
RIPK3	activates	gene	0.70
endothelial cells	activates	cell_type	0.70
PYCARD	activates	gene	0.70
NLRP3	disrupts	gene	0.70
STING1	regulates	gene	0.70
STAT3	activates	gene	0.70
stem cells	expressed_in	cell_type	0.70
NRBF2	activates	gene	0.70
PI3K	activates	gene	0.70
PI3K-AKT-mTOR signaling	participates_in	pathway	0.70
STING1	activates	gene	0.70
microglia	expressed_in	cell_type	0.70
neurodegeneration	disrupts	disease	0.70
Alzheimer's disease	activates	disease	0.70
macrophages	expressed_in	cell_type	0.70
PRKN	regulates	gene	0.70
Neurodegeneration	therapeutic_target	disease	0.65
Parkinson	regulates	disease	0.65
Neuroinflammation	therapeutic_target	disease	0.65
Parkinson	therapeutic_target	disease	0.65
Alzheimer	therapeutic_target	disease	0.65
Cardiovascular	causes	disease	0.65

Incoming (518)

Source	Relation	Type	Str
NBR1	regulates	gene	0.80
LC3	regulates	gene	0.80
ERN1	regulates	gene	0.80
rapamycin	targets	drug	0.80
LC3	activates	gene	0.80
ERN1	activates	gene	0.80
DDIT3	activates	gene	0.70
ATP	activates	gene	0.70
EIF2AK3	activates	gene	0.70
ATG	activates	gene	0.70
DNA	activates	gene	0.70
FIP200	activates	gene	0.70
BECN1	activates	gene	0.70
NDP52	regulates	gene	0.70
DDIT3	regulates	gene	0.70
MTOR	regulates	gene	0.70
FIP200	regulates	gene	0.70
CALCOCO2	regulates	gene	0.70
DNA	regulates	gene	0.70
ATP	regulates	gene	0.70
MAPK	regulates	gene	0.70
ATG	regulates	gene	0.70
EIF2AK3	regulates	gene	0.70
BCL2	regulates	gene	0.70
JNK	regulates	gene	0.70
JNK	activates	gene	0.70
NBR1	activates	gene	0.70
MAP1LC3	regulates	gene	0.70
MTOR	activates	gene	0.70
MAPK	activates	gene	0.70
IL1B	inhibits	gene	0.60
UBIQUITIN	activates	gene	0.60
NAD	associated_with	gene	0.60
TNF	associated_with	gene	0.60
NEURODEGENERATION	inhibits	gene	0.60
AUTOPHAGY	associated_with	gene	0.60
IL-1	associated_with	gene	0.60
NFKB	associated_with	gene	0.60
ATG5	associated_with	gene	0.60
AIM2	associated_with	gene	0.60
MARCH7	associated_with	gene	0.60
LAMP1	associated_with	gene	0.60
ATG	interacts_with	gene	0.60
PYCARD	associated_with	gene	0.60
INFLAMMATION	activates	gene	0.60
AUTOPHAGY	activates	gene	0.60
ATP	associated_with	gene	0.60
ATG5	activates	gene	0.60
NLRP3	activates	gene	0.60
PEX3	interacts_with	gene	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming	0.924	neurodegeneration	What are the mechanisms by which gut mic
Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-S	0.822	neurodegeneration	What are the mechanisms by which gut mic
NLRP3 inflammasome amplification across AD and PD proteinopa	0.800	multi	Cross-disease neurodegeneration mechanis
NLRP3 Inhibition (H7): Downstream Inflammatory Reversal	0.780	neurodegeneration	Does restoring neuronal AMPK activity re
NLRP3 Inflammasome Inhibition for Neuroprotection in Parkins	0.720	neurodegeneration	Test

NLRP3 Inflammasome Lock Perpetuates Senescence-Associated In	0.720	neurodegeneration	What molecular mechanisms drive microgli
NLRP3/Mitophagy Coupling Modulation	0.681	neuroinflammation	Immune atlas neuroinflammation analysis
C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque Macropha	0.631	neuroinflammation	What are the specific molecular mechanis
Galectin-3 deletion attenuates NLRP3 inflammasome activation	0.625	neuroscience	Lysosomal dysfunction and cathepsin leak
NLRP3 Inflammasome Priming Converts SCFA-Sensitive Pyroptosi	0.620	neurodegeneration	How does gut microbiome dysbiosis contri
Selective cathepsin B inhibition prevents cathepsin leakage-	0.620	neuroscience	Lysosomal dysfunction and cathepsin leak
LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasom	0.617	neurodegeneration	How do perivascular cells specifically r
The most realistic translational use of physiological SCFAs	0.610	neurodegeneration	Do physiological concentrations of SCFAs
NLRP3 Inflammasome Inhibition Prevents Synapse Loss via IL-1	0.610	neurodegeneration	Test Preregistration Analysis
Intermittent HBOT (2.0 ATA, 60 min, 3x/week) suppresses NLRP	0.590	neurodegeneration	What are the optimal oxygen pressure, du
LAMP-2 replacement therapy prevents lysosomal membrane perme	0.580	neuroscience	Lysosomal dysfunction and cathepsin leak
CX3CR1-Negative Trem2-High Microglial Subset Mediates Female	0.570	neuroinflammation	How do regional, age, and sex-dependent
NLRP3 Inflammasome Chromatin Priming Through H3K27ac Accumul	0.566	developmental-neurobiology	Do perinatal immune challenges create pe
NLRP3 Inflammasome Blockade as Upstream Intervention to Prev	0.566	neurodegeneration	Why have numerous phase 3 clinical trial
P2X7R PET Imaging for NLRP3 Inflammasome-Associated Priming	0.563	biomarkers	What biomarkers can reliably detect micr
Temporal NLRP3 Inhibition During SPP1-Driven Microglial Acti	0.551	neuroinflammation	What molecular mechanisms mediate SPP1-i
Physiological SCFAs may worsen alpha-synuclein pathology thr	0.550	neurodegeneration	Do physiological concentrations of SCFAs
Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhanc	0.496	neuroinflammation	What molecular mechanisms mediate SPP1-i
TFEB-Mediated Lysosomal Biogenesis Enhancement for NLRP3 Inf	0.485	neuroinflammation	Immune atlas neuroinflammation analysis
Sub-antidepressant Doses Suppress NLRP3 Inflammasome via P2X	0.465	-	What is the minimum effective dose of tr
STING-Mediated NLRP3 Inflammasome Priming in ALS Microglia	0.380	neuroinflammation	Immune atlas neuroinflammation analysis
NLRP3/Autophagy Flux Enhancement in Astrocytes	0.380	neuroinflammation	Immune atlas neuroinflammation analysis
Circulating hs-CRP as Disease-Modifying Target via Astrocyti	0.380	immunomics	Systemic immune profiling in neurodegene
NLRP3 Inflammasome Suppression via Selective Caspase-1 Inhib	0.105	neurodegeneration	Neuroinflammation Biomarker Panel for Ea
Microglial NLRP3 Inflammasome as Circadian-Specific Drug Tar	0.000	-	Can circadian interventions selectively

Mentioning Analyses (1)

Scientific analyses that reference this entity

Lysosomal dysfunction and cathepsin leakage in Alzheimer disease progression

neuroscience | 2026-04-04 | 7 hypotheses Top: 0.679

Experiments (4)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Molecular characterization of RBG-NLRP3 binding interaction	exploratory	atherosclerosis	0.900	purified proteins and molecula	proposed	N/A
Leukocyte gene expression analysis in COVID-19 patients	exploratory	COVID-19	0.900	human leukocytes from COVID-19	proposed	N/A
RBG effects on macrophage polarization and foam cell formation	exploratory	atherosclerosis	0.850	primary macrophages	proposed	N/A
Transcriptomic analysis of RBG effects on inflammatory gene expression	exploratory	atherosclerosis	0.800	ApoE-/- mice and cell cultures	proposed	N/A

Related Papers (14)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025
Enhancing TREM2 expression activates microglia and modestly mitigates tau pathol [PMID:40122810]	["Chen Kai", "Li Fuyao", "Zhang Shuwen",	Journal of neuroinflammation	2025
Interaction between autophagy and the NLRP3 inflammasome in Alzheimer's and Park [PMID:36262883]	Unknown	Frontiers in aging neuroscienc	2023
Inhibition of autophagy in microglia and macrophages exacerbates innate immune r [PMID:36652438]	Hegdekar N, Sarkar C, Bustos S, Ritzel R	Autophagy	2023
Parkin regulates microglial NLRP3 and represses neurodegeneration in Parkinson's [PMID:37029500]	Yan YQ, Zheng R, Liu Y, Ruan Y, Lin ZH,	Aging cell	2023
Microglial NLRP3 inflammasome activates neurotoxic astrocytes in depression-like [PMID:36288697]	Li S, Fang Y, Zhang Y, Song M, Zhang X,	Cell reports	2022
Biomarker of Neuroinflammation in Parkinson's Disease. [PMID:35456966]	Liu TW, Chen CM, Chang KH	Int J Mol Sci	2022
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020
Neurodegeneration and Inflammation-An Interesting Interplay in Parkinson's Disea [PMID:33182554]	Marogianni C, Sokratous M, Dardiotis E,	International journal of molec	2020
NLRP3 inflammasome activation drives tau pathology. [PMID:31748742]	["Ising C", "Venegas C", "Zhang S", "Sch	Nature	2019
Multiple Sclerosis Pathology. [PMID:29358320]	Lassmann H	Cold Spring Harbor perspective	2018
Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodeg [PMID:30381407]	Gordon R, Albornoz EA, Christie DC, Lang	Science translational medicine	2018
NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS [PMID:23254930]	Heneka MT, Kummer MP, Stutz A, Delekate	Nature	2013
NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS [PMID:23254930]	["Heneka Michael T", "Kummer Markus P",	Nature	2013

Debates (1)

Multi-agent debates referencing this entity

Lysosomal membrane permeabilization releasing cathepsins triggers NLRP3 inflamma

closed · Rounds: 4 · Score: 0.76 · 2026-04-22

Related Research

Hypotheses and analyses mentioning NLR in their description or question text

NLRP3 Inflammasome Lock Perpetuates Senescence-Associated Inflammasome Phenotype

Score: 0.720 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome represen

NLRP3/Mitophagy Coupling Modulation

Score: 0.681 · neuroinflammation · 2026-04-12

## Mechanistic Overview NLRP3/Mitophagy Coupling Modulation starts from the claim that modulating NLRP3 within the disea

C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque Macrophages

Score: 0.631 · neuroinflammation · 2026-04-21

**Molecular Mechanism and Rationale** The C1Q complement system component represents a critical bridge between innate i

Galectin-3 deletion attenuates NLRP3 inflammasome activation downstream of lysos

Score: 0.625 · neuroscience · 2026-04-22

**Molecular Mechanism and Rationale** Galectin-3 (LGALS3) functions as a critical molecular sensor and platform orchest

NLRP3 Inflammasome Priming Converts SCFA-Sensitive Pyroptosis into Chronic IL-1β

Score: 0.620 · neurodegeneration · 2026-04-26

Gut-derived bacterial components (LPS, MDP) provide Signal 1 for NLRP3 inflammasome priming via TLR4/TLR2/NOD2, inducing

Selective cathepsin B inhibition prevents cathepsin leakage-mediated NLRP3 infla

Score: 0.620 · neuroscience · 2026-04-22

## Mechanistic Overview Selective cathepsin B inhibition prevents cathepsin leakage-mediated NLRP3 inflammasome activati

LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP

Score: 0.617 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The proposed LRP1/NLRP3/IL-1β cascade represents a critical mechanistic link betw

The most realistic translational use of physiological SCFAs is as an adjunct to

Score: 0.610 · neurodegeneration · 2026-04-24

Physiological SCFA elevation may generate a weak, context-dependent signal that is insufficient alone but could become b

NLRP3 Inflammasome Inhibition Prevents Synapse Loss via IL-1β Suppression

Score: 0.610 · neurodegeneration · 2026-04-28

NLRP3 inflammasome activation releases IL-1β, driving complement cascade upregulation and synapse elimination. MCC950 or

Intermittent HBOT (2.0 ATA, 60 min, 3x/week) suppresses NLRP3 inflammasome and s

Score: 0.590 · neurodegeneration · 2026-04-25

This hypothesis proposes that HBOT reduces ROS-mediated NF-κB activation and NLRP3 inflammasome assembly, promoting anti

LAMP-2 replacement therapy prevents lysosomal membrane permeabilization and down

Score: 0.580 · neuroscience · 2026-04-22

## Mechanistic Overview LAMP-2 replacement therapy prevents lysosomal membrane permeabilization and downstream NLRP3 act

CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Estr

Score: 0.570 · neuroinflammation · 2026-04-22

## Mechanistic Overview CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Estrogen Receptor-al

NLRP3 Inflammasome Chromatin Priming Through H3K27ac Accumulation

Score: 0.566 · developmental-neurobiology · 2026-04-21

## Mechanistic Overview NLRP3 Inflammasome Chromatin Priming Through H3K27ac Accumulation starts from the claim that mod

NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP Amplificati

Score: 0.566 · neurodegeneration · 2026-04-16

## Mechanistic Overview NLRP3 Inflammasome Blockade as Upstream Intervention to Prevent SASP Amplification starts from t

P2X7R PET Imaging for NLRP3 Inflammasome-Associated Priming

Score: 0.563 · biomarkers · 2026-04-22

## Mechanistic Overview P2X7R PET Imaging for NLRP3 Inflammasome-Associated Priming starts from the claim that modulatin

NLR

Understanding Entity Pages

Summary

Wiki Pages (20)

Validated Hypothesis: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration

Validated Hypothesis: Astrocyte-Intrinsic NLRP3 Inflammasome Activation by Alpha-Synuclein Aggregates Drives Non-Cell-Autonomous Neurodegeneration

NLRP3 Inflammasome Activation Pathway in Neurodegeneration

NLRP3 Inflammasome Hypothesis in Parkinson's Disease

NLRP3 Inflammasome Pathway in Neurodegeneration

NLRP3 Senomorphic Cycling Therapy

NLRP3 Inflammasome Inhibitors for Parkinson's Disease

NLRC5 — NLR Family CARD Domain Containing 5

NLRP7 — NLR Family Pyrin Domain Containing 7

NLRP3-Coupled Senomorphic Cycling Therapy

NLRP2 — NLR Family Pyrin Domain Containing 2

NLRP3 Inflammasome Inhibitors for Neurodegenerative Diseases

NLRP3 Inhibitors for Neurodegeneration

NLRP3 Inflammasome Pathway in Alzheimer's Disease

NLRC3 — NLR Family CARD Domain Containing 3

NLRP3 Inflammasome Modulation for Parkinson's Disease

NLRP6 Protein (NACHT, LRR and PYD Domains-Containing Protein 6)

NLRP3 Inflammasome-Activated Microglia

NLRP7 Protein — NLR Family Pyrin Domain Containing 7

Innate Immune Reprogramming: NLRP3 + CD47 Checkpoint Blockade