gene

NRF2

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about NRF2: 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.

3519Connections

15Hypotheses

14Analyses

50Outgoing

50Incoming

0Experiments

15Debates

Summary

NRF2 is a gene implicated in neurodegeneration research. Key relationships include: activates, regulates, inhibits. Associated with ALS, ALZHEIMER'S DISEASE, Aging. Connected to 1652 entities in the SciDEX knowledge graph.

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🧬 Gene Info

Gene Symbol	NRF2
Chromosome	2q31.2
Protein Family	Cap'n'Collar (CNC) bZIP transcription factor
Function	Basal state: Keap1 homodimer binds NRF2 via the DLG and ETGE motifs, serving as a substrate adapter for the Cul3-RING ubiquitin E3 ligase complex.
Molecular Weight	68 kDa
Amino Acids	605 aa
Pathways	Akt, Apoptosis, Autophagy, Cell Cycle, Chaperone
GeneCards	NRF2
Human Protein Atlas	NRF2
Associated Diseases	aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	4-octyl itaconate, 4OI, ALGERNON2, Alpha-Tocopherol, Artesunate, ATORVASTATIN
Interactions	ABCG2, ACETYLCHOLINE, ACHE, ACOD1, ACSL4, Actin
KG Connections	3455 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

Wiki Pages (11)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    NRF2["NRF2 Transcription Factor"] -->|"Inhibited by"| KEAP1["KEAP1 Repressor"]
    NRF2 -->|"Activates"| ARE["Antioxidant Response Element"]
    NRF2 -->|"Regulates"| OX["Oxidative Stress Response"]
    NRF2 -->|"Inhibits"| INFLAM["Inflammation"]
    NRF2 -->|"Regulates"| NFKB["NF-kappaB Pathway"]
    ARE -->|"Induces"| HMOX1["HMOX1"]
    ARE -->|"Induces"| NQO1["NQO1"]
    ARE -->|"Induces"| SOD["SOD"]
    ARE -->|"Induces"| GCLC["GCLC"]
    ARE -->|"Induces"| GCLM["GCLM"]
    ARE -->|"Induces"| SRXN1["SRXN1"]
    ARE -->|"Induces"| TXNRD1["TXNRD1"]
    GCLC -->|"Synthesizes"| GSH["Glutathione"]
    GCLM -->|"Synthesizes"| GSH
    NRF2 -->|"Implicated in"| ND["Neurodegeneration"]
    NRF2 -->|"Associated with"| CCRCC["Clear Cell RCC"]

    style NRF2 fill:#1b5e20,color:#e0e0e0
    style KEAP1 fill:#b71c1c,color:#e0e0e0
    style ARE fill:#0d47a1,color:#e0e0e0

Outgoing (2049)

Target	Relation	Type	Str
OXIDATIVE STRESS	activates	gene	1.00
STROKE	associated_with	disease	1.00
Inflammation	inhibits	disease	1.00
OXIDATIVE STRESS	regulates	gene	1.00
Nf-Κb	inhibits	pathway	1.00
MITOCHONDRIA	activates	gene	1.00
Aging	therapeutic_target	disease	1.00
Cardiac	activates	disease	1.00
Apoptosis	inhibits	pathway	1.00
Cancer	activates	disease	1.00
Pi3K/Akt	activates	pathway	1.00
NEUROINFLAMMATION	activates	gene	1.00
Cancer	inhibits	disease	1.00
OXIDATIVE STRESS	associated_with	gene	1.00
Ferroptosis	activates	pathway	1.00
Nf-Κb	activates	pathway	1.00
Alzheimer	activates	disease	1.00
Parkinson	therapeutic_target	disease	1.00
AUTOPHAGY	activates	gene	1.00
Inflammation	regulates	disease	1.00
Als	regulates	disease	1.00
Parkinson	activates	disease	1.00
Apoptosis	regulates	pathway	1.00
Aging	regulates	disease	1.00
OXIDATIVE STRESS	inhibits	gene	1.00
Mapk	inhibits	pathway	1.00
AKT	activates	protein	1.00
Cancer	therapeutic_target	disease	1.00
Carcinoma	activates	disease	1.00
Tumor	inhibits	disease	1.00
Tumor	activates	disease	1.00
Ferroptosis	inhibits	pathway	1.00
Stroke	activates	disease	1.00
Autophagy	activates	pathway	1.00
Apoptosis	activates	pathway	1.00
Oxidative Stress	activates	pathway	1.00
Als	activates	disease	1.00
Als	inhibits	disease	1.00
Neuroinflammation	activates	disease	1.00
Oxidative Stress	regulates	pathway	1.00
Cancer	regulates	disease	1.00
Nf-Κb	regulates	pathway	1.00
Als	therapeutic_target	disease	1.00
Inflammation	therapeutic_target	disease	1.00
Neurodegeneration	activates	disease	1.00
ferroptosis	regulates	process	1.00
SOD1	associated_with	gene	1.00
Autophagy	regulates	pathway	1.00
Inflammation	activates	disease	1.00
PARKINSON'S DISEASE	associated_with	disease	1.00

Incoming (1470)

Source	Relation	Type	Str
KEAP1	regulates	gene	1.00
NEURODEGENERATION	activates	gene	1.00
HO-1	activates	gene	1.00
PI3K	activates	gene	1.00
GPX4	activates	gene	1.00
P62	activates	protein	1.00
NEURODEGENERATION	associated_with	gene	1.00
CYTOKINES	activates	gene	1.00
APOPTOSIS	associated_with	gene	1.00
KEAP1	activates	gene	1.00
SQSTM1	activates	gene	1.00
GENES	activates	gene	1.00
GPX4	inhibits	gene	1.00
GENES	regulates	gene	1.00
ALZHEIMER'S DISEASE	associated_with	disease	1.00
TMEM16F	regulates	gene	1.00
OXIDATIVE STRESS	associated_with	gene	1.00
NF-ΚB	regulates	gene	1.00
OXIDATIVE STRESS	regulates	gene	1.00
INFLAMMATION	therapeutic_target	gene	1.00
INFLAMMATION	inhibits	gene	1.00
INFLAMMATION	activates	phenotype	1.00
INFLAMMATION	regulates	gene	1.00
OXIDATIVE STRESS	inhibits	gene	1.00
APOPTOSIS	regulates	gene	1.00
CANCER	activates	gene	1.00
NF-ΚB	activates	gene	1.00
ROS	activates	phenotype	1.00
ROS	regulates	gene	1.00
NEURODEGENERATIVE DISEASES	activates	gene	1.00
CANCER	therapeutic_target	gene	1.00
FERROPTOSIS	inhibits	gene	1.00
CANCER	regulates	gene	1.00
HO-1	inhibits	gene	1.00
KEAP1	inhibits	protein	1.00
NF-KB	associated_with	protein	1.00
OXIDATIVE STRESS	activates	gene	1.00
GENES	associated_with	gene	1.00
KEAP1	associated_with	gene	1.00
PARKINSON'S DISEASE	therapeutic_target	gene	1.00
BCL-2	activates	gene	1.00
OXIDATIVE STRESS	therapeutic_target	gene	1.00
PARKINSON'S DISEASE	activates	gene	1.00
ROS	inhibits	gene	1.00
HO-1	regulates	gene	1.00
NEURODEGENERATIVE DISEASES	regulates	gene	1.00
PARKINSON	therapeutic_target	gene	1.00
CANCER	inhibits	gene	1.00
FERROPTOSIS	activates	gene	0.98
M102	activates	drug	0.95

Targeting Hypotheses (15)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
NRF2 failure lowers antioxidant reserve and permits recurren	0.740	neurodegeneration	What mechanisms drive the self-amplifyin
NRF2 Activation Provides Neuroprotection Across ALS, AD, and	0.710	neurodegeneration	Test Preregistration Analysis
NRF2-Mediated Proteostatic Convergence: Shared Oxidative Str	0.700	neurodegeneration	-
Endothelial NRF2 Activation as a Master Switch for Post-CA B	0.689	neurodegeneration	Can ferroptosis inhibitors prevent BBB d
NRF2-KEAP1 Pathway Activation to Coordinate Multi-Layer Anti	0.650	-	Ferroptosis in ALS and motor neuron dise

HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf	0.640	neurodegeneration	What are the optimal oxygen pressure, du
Nrf2 Pathway Activation Compensates for Progranulin Haploins	0.630	neurodegeneration	Test
NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/	0.602	neurodegeneration	What are the optimal oxygen pressure, du
oxLDL/LOX-1/ROS Signaling Induces P2RY12 via Nrf2 Activation	0.550	neurodegeneration	What determines P2RY12 receptor expressi
NRF2 pathway activation to reduce mutant huntingtin aggregat	0.540	neurodegeneration	Test
NRF2 Activation to Counteract Oxidative Stress from RGS6 Def	0.518	neurodegeneration	Does RGS6 upregulation or D2 autorecepto
Metabolic Accumulation (Ammonia/Manganese) Triggers IBA1 Dow	0.517	neuroinflammation	What causes IBA1 low/negative microglia
Nrf2-NF-κB Oscillatory Circuit Modulation	0.000	-	Astrocyte Reactivity Subtypes in Neurode
NRF2 Pathway Activation for Neuroprotection	0.000	-	4R-tau strain-specific spreading pattern
Temporal Nrf2-mTOR Dual Switch Therapy	0.000	-	Astrocyte reactivity subtypes in neurode

Mentioning Analyses (14)

Scientific analyses that reference this entity

Oxidative Stress Upstream of TDP-43 Mislocalization in ALS Motor Neurons

neurodegeneration | 2026-04-27 | 0 hypotheses

Test Preregistration Analysis

neurodegeneration | 2026-04-27 | 7 hypotheses Top: 0.710

What is the optimal dosage and timing of melatonin administration for AD prevent

neurodegeneration | 2026-04-26 | 7 hypotheses Top: 0.735

Does RGS6 upregulation or D2 autoreceptor modulation prevent neurodegeneration i

neurodegeneration | 2026-04-17 | 7 hypotheses Top: 0.559

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

neurodegeneration | 2026-04-16 | 7 hypotheses Top: 0.680

Experiments (0)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
No experiments found

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (15)

Multi-agent debates referencing this entity

Test question for preregistration

closed · Rounds: 4 · Score: 0.77 · 2026-04-28

Can targeting oxidative stress pathways (NRF2, SOD1, mitochondrial ROS) upstream

closed · Rounds: 6 · Score: 0.62 · 2026-04-27

What is the optimal dosage and timing of melatonin administration for AD prevent

closed · Rounds: 4 · Score: 1.00 · 2026-04-26

The study shows P2RY12 regulates VSMC foam cell formation but doesn't explain wh

closed · Rounds: 4 · Score: 0.66 · 2026-04-21

The core debate question remains unresolved - whether intrinsic tau conformation

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

Which transcription factors drive the gene regulatory networks that distinguish

closed · Rounds: 4 · Score: 0.70 · 2026-04-21

The debate revealed a critical gap: while PINK1/PARKIN deficiency correlates wit

closed · Rounds: 4 · Score: 0.50 · 2026-04-20

While RGS6 deficiency causes Parkinson's-like pathology, whether enhancing RGS6

closed · Rounds: 4 · Score: 0.50 · 2026-04-18

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

closed · Rounds: 5 · Score: 0.59 · 2026-04-16

Is REST the master regulator of neuronal vulnerability in AD, or is it one of se

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

Related Research

Hypotheses and analyses mentioning NRF2 in their description or question text

NRF2

Understanding Entity Pages

Summary

Wiki Pages (11)

NRF2 Gene

NRF2 Oxidative Stress Pathway

NRF2 Activator Therapy for Neurodegeneration

NRF2 Activators for Parkinson's Disease

NRF2 Signaling Pathway in Neurodegeneration

NRF2 — Nuclear Factor Erythroid 2-Related Factor 2

Parkinson's Disease NRF2-Keap1 Pathway Therapy Companies

NRF2 Therapeutics: Investment Landscape Analysis

NRF2-KEAP1 Oxidative Stress Response Pathway

NRF2 Activators in Neurodegenerative Disease

NRF2 Activator Therapy

Pathway Diagram

Outgoing (2049)

Incoming (1470)

Targeting Hypotheses (15)

Mentioning Analyses (14)

Oxidative Stress Upstream of TDP-43 Mislocalization in ALS Motor Neurons

Test Preregistration Analysis

What is the optimal dosage and timing of melatonin administration for AD prevent

Does RGS6 upregulation or D2 autoreceptor modulation prevent neurodegeneration i

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

Gene Regulatory Network Inference in Alzheimer's Disease

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

Do PINK1/PARKIN pathway enhancements rescue excitatory neuron vulnerability or e

Do tau strains or regional cellular environments primarily drive PSP vs CBD path

What molecular mechanisms drive tissue-specific phenotypes in Mendelian neurolog

What determines P2RY12 receptor expression/activity specifically in VSMCs during

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

Neuroinflammation resolution mechanisms and pro-resolving mediators

Experiments (0)

Related Papers (0)

Debates (15)

Test question for preregistration

Can targeting oxidative stress pathways (NRF2, SOD1, mitochondrial ROS) upstream

What is the optimal dosage and timing of melatonin administration for AD prevent

The study shows P2RY12 regulates VSMC foam cell formation but doesn't explain wh

The core debate question remains unresolved - whether intrinsic tau conformation

Which transcription factors drive the gene regulatory networks that distinguish

The debate revealed a critical gap: while PINK1/PARKIN deficiency correlates wit

While RGS6 deficiency causes Parkinson's-like pathology, whether enhancing RGS6

Ferroptosis in ALS and motor neuron disease: GPX4, lipid peroxidation, and iron

Is REST the master regulator of neuronal vulnerability in AD, or is it one of se

Related Research

HBOT at 1.5 ATA for 60 min induces hormetic response via Nrf2 activation, enhanc

Nrf2 Pathway Activation Compensates for Progranulin Haploinsufficiency in FTD-GR

NRF2-Mediated Metabolic Reprogramming: HBOT as Direct NAMPT/SIRT1 Activator for

oxLDL/LOX-1/ROS Signaling Induces P2RY12 via Nrf2 Activation

NRF2 pathway activation to reduce mutant huntingtin aggregates and oxidative str

NRF2 Activation to Counteract Oxidative Stress from RGS6 Deficiency

Metabolic Accumulation (Ammonia/Manganese) Triggers IBA1 Downregulation via NRF2

Nrf2-NF-κB Oscillatory Circuit Modulation

NRF2 Pathway Activation for Neuroprotection

Temporal Nrf2-mTOR Dual Switch Therapy