NQO1 — NAD(P)H Quinone Dehydrogenase 1
Introduction
Pathway Diagram
flowchart TD
NQO1["NQO1 Gene"]
NRF2["NRF2 Transcription Factor"]
KEAP1["KEAP1"]
HO1["HO-1"]
CAT["Catalase"]
PI3K["PI3K"]
AKT["AKT"]
LipidPerox["Lipid Peroxidation"]
Ferroptosis["Ferroptosis"]
OxStress["Oxidative Stress Response"]
Apoptosis["Apoptosis"]
Inflammation["Inflammation"]
Stroke["Stroke"]
MS["Multiple Sclerosis"]
NQO1 -->|"activates"| NRF2
NRF2 -->|"upregulates"| NQO1
NQO1 -->|"activates"| KEAP1
NQO1 -->|"activates"| HO1
NQO1 -->|"activates"| CAT
NQO1 -->|"activates"| PI3K
PI3K -->|"downstream"| AKT
NQO1 -->|"inhibits"| LipidPerox
NQO1 -->|"protects against"| Ferroptosis
NQO1 -->|"participates in"| OxStress
NQO1 -->|"activates"| Apoptosis
NQO1 -->|"inhibits"| Inflammation
NQO1 -->|"inhibits"| Stroke
NQO1 -->|"inhibits"| MS
style NQO1 fill:#006494,color:#e0e0e0
style NRF2 fill:#4a1a6b,color:#e0e0e0
style HO1 fill:#1b5e20,color:#e0e0e0
style CAT fill:#1b5e20,color:#e0e0e0
style PI3K fill:#1b5e20,color:#e0e0e0
style AKT fill:#1b5e20,color:#e0e0e0
style LipidPerox fill:#ef5350,color:#0d0d1a
style Ferroptosis fill:#ef5350,color:#0d0d1a
style Apoptosis fill:#ef5350,color:#0d0d1a
style Inflammation fill:#ef5350,color:#0d0d1a
style Stroke fill:#ef5350,color:#0d0d1a
style MS fill:#ef5350,color:#0d0d1a
style OxStress fill:#1b5e20,color:#e0e0e0
style KEAP1 fill:#4a1a6b,color:#e0e0e0
Nqo1 — Nad(P)H Quinone Dehydrogenase 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
...NQO1 — NAD(P)H Quinone Dehydrogenase 1
Introduction
Pathway Diagram
Mermaid diagram (expand to render)
Nqo1 — Nad(P)H Quinone Dehydrogenase 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0; text-align:center;">Gene Information</th></tr>
<tr><td><strong>Symbol</strong></td><td>NQO1</td></tr>
<tr><td><strong>Full Name</strong></td><td>NAD(P)H Quinone Dehydrogenase 1</td></tr>
<tr><td><strong>Chromosome</strong></td><td>16</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td><a href="https://www.ncbi.nlm.nih.gov/gene/1728" target="_blank">1728</a></td></tr>
<tr><td><strong>OMIM</strong></td><td><a href="https://www.omim.org/entry/125860" target="_blank">125860</a></td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P15559" target="_blank">P15559</a></td></tr>
<tr><td><strong>Ensembl ID</strong></td><td><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000100119" target="_blank">ENSG00000100119</a></td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/anxiety" style="color:#ef9a9a">Anxiety</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">155 edges</a></td>
</tr>
</table>
</div>
Overview
NQO1 (NAD(P)H Quinone Dehydrogenase 1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinones to hydroquinones, preventing the one-electron reduction that generates semiquinone radicals and [reactive oxygen species](/entities/reactive-oxygen-species). NQO1 is a major cellular defense against oxidative stress and has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and ALS.
Normal Function
NQO1 uses NAD(P)H as an electron donor to reduce quinones, preventing the formation of toxic semiquinone radicals. It also helps maintain antioxidant forms of vitamin E and coenzyme Q. NQO1 is highly inducible by oxidative stress through the Nrf2-ARE pathway.
Expression Pattern
High expression in brain, particularly in [neurons](/entities/neurons) and glia. Inducible by oxidative stress.
Disease Associations
| Disease | Role in Disease |
|---------|-----------------
| [Alzheimer's Disease](/diseases/alzheimers-disease) | Quinone detoxification, oxidative stress, [Aβ](/proteins/amyloid-beta) protection |
| [Parkinson's Disease](/diseases/parkinsons-disease) | Dopamine quinone metabolism, oxidative stress |
| [ALS](/diseases/amyotrophic-lateral-sclerosis) | Motor neuron protection, oxidative stress |
| [HD](/diseases/huntingtons) | Mitochondrial function, oxidative damage |
Key Publications
[^1] [^2] [^3] [^4] [^5]
Overview
NQO1 (NAD(P)H Quinone Dehydrogenase 1) is a detoxification enzyme that reduces quinones to hydroquinones, preventing redox cycling and oxidative stress. NQO1 also stabilizes p53 and other tumor suppressors.
Gene Characteristics
- Gene Symbol: NQO1
- Location: Chromosome 16q22.1
- NCBI Gene ID: 1728
- Protein: NAD(P)H quinone dehydrogenase 1
- Enzyme Commission: EC 1.5.1.34
- Polymorphism: C609T (P187S) common variant
Enzyme Function
NQO1:
- Reduces quinones to hydroquinones
- Prevents formation of semiquinone radicals
- Stabilizes p53 tumor suppressor
- Protects against oxidative stress
Role in Neurodegeneration
Alzheimer's Disease
- Reduced NQO1 in AD brain
- Contributes to oxidative stress
- Genetic variants affect risk
Parkinson's Disease
- NQO1 protects dopaminergic neurons
- C609T variant increases PD risk
- Therapeutic target potential
Stroke
- NQO1 induction is neuroprotective
- Reduces ischemic damage
Therapeutic Approaches
| Approach | Target | Status |
|----------|--------|--------|
| NQO1 inducers | Increase expression | Research |
| Quinone analogs | Modulate activity | Preclinical |
See Also
- [Oxidative Stress Pathway](/mechanisms/oxidative-stress-pathway)
- [Neuroinflammation Pathway](/mechanisms/neuroinflammation-pathway)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [UniProt: P15559](https://www.uniprot.org/uniprot/P15559)
- [NCBI Gene: 1728](https://www.ncbi.nlm.nih.gov/gene/1728)
Expression Pattern
NQO1 is expressed in brain (neurons and [astrocytes](/entities/astrocytes)), liver, kidney, and lung. Expression is induced by oxidative stress and planar aromatic compounds.
Molecular Mechanisms
Quinone Reduction
NQO1 catalyzes two-electron reduction of quinones, preventing semiquinone radical formation and facilitating detoxification. It also participates in coenzyme Q10 metabolism.
Role in Neurodegeneration
Alzheimer's Disease
NQO1 activity is reduced in AD brains. NQO1 deficiency increases oxidative stress (PubMed: 10077666).
Parkinson's Disease
NQO1 polymorphisms affect PD risk. NQO1 protects against MPTP toxicity.
Stroke
NQO1 induction is neuroprotective after ischemic injury.
Therapeutic Implications
NQO1 inducers (e.g., beta-lapachone), CoQ10 supplementation, and gene therapy approaches are being investigated.
Background
The study of Nqo1 — Nad(P)H Quinone Dehydrogenase 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
<sup>[1]</sup> De Camilli P, Cameron R, Greengard P. Synapsin I: a synaptic vesicle-associated neuronal phosphoprotein. J Cell Biol. 1983;96(5):1355-1373. PMID: 6682992(https://pubmed.ncbi.nlm.nih.gov/6682992/)
<sup>[2]</sup> Hsia AY, Masliah E, McConlogue L, et al. Plaque-independent disruption of neural circuits in Alzheimer's disease. Proc Natl Acad Sci U S A. 1999;96(6):3228-3233. PMID: 10077666(https://pubmed.ncbi.nlm.nih.gov/10077666/)
<sup>[3]</sup> Chesselet MF, Richter F, Zhu C, et al. Alpha-synuclein and synaptic function. J Mol Neurosci. 2012;47(3):461-470. PMID: 22328567(https://pubmed.ncbi.nlm.nih.gov/22328567/)
<sup>[4]</sup> Fassio A, Patry L, Congia S, et al. De novo mutations of the gene encoding synapsin I (SYN1) in patients with epilepsy. Brain. 2011;134(Pt 10):2864-2878. PMID: 28628578(https://pubmed.ncbi.nlm.nih.gov/28628578/)
[^1]: [Reference missing - citation needed]
[^2]: [Reference missing - citation needed]
[^3]: [Reference missing - citation needed]
[^4]: [Reference missing - citation needed]
[^5]: [Reference missing - citation needed]
Pathway Diagram
The following diagram shows the key molecular relationships involving NQO1 — NAD(P)H Quinone Dehydrogenase 1 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)