NEIL1 — Nei Endonuclease VIII-Like 1
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">NEIL1 — Nei Endonuclease VIII-Like 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>NEIL1</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Nei Endonuclease VIII-Like 1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>15q24.2</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>57478</td>
</tr>
<tr>
<td class="label">OMIM ID</td>
<td>608747</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000140323</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q9Y3X0</td>
</tr>
<tr>
<td class="label">Lesion</td>
<td>Type</td>
</tr>
<tr>
<td class="label">8-oxoguanine (8-oxoG)</td>
<td>Oxidative</td>
</tr>
<tr>
<td class="label">5-hydroxyuracil (5-OHU)</td>
<td>Oxidative</td>
</tr>
<tr>
<td class="label">Thymine glycol (Tg)</td>
<td>Oxidative</td>
</tr>
<tr>
<td class="label">FapyGuanine (FapyG)</td>
<td>Oxidative</td>
</tr>
<tr>
<td class="label">5-hydroxycytosine (5-OHC)</td>
<td>Oxidative</td>
</tr>
<tr>
<td class="label">Tissue</td>
<td>Expression Level</td>
</tr>
<tr>
<td class="label">Brain</td>
<td>High</td>
</tr>
<tr>
<td class="label">Liver</td>
<td>High</td>
</tr>
<tr>
<td class="label">Kidney</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Heart</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Skeletal muscle</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Strategy</td>
<td>Approach</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>AAV-NEIL1 delivery</td>
</tr>
<tr>
<td class="label">Small molecules</td>
<td>NEIL1 activators</td>
</tr>
<tr>
<td class="label">Antioxidants</td>
<td>Reduce substrate load</td>
</tr>
<tr>
<td class="label">BER enhancers</td>
<td>Enhance repair capacity</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/carcinoma" style="color:#ef9a9a">Carcinoma</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/senescence" style="color:#ef9a9a">Senescence</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">30 edges</a></td>
</tr>
</table>
Neil1 — Nei Endonuclease Viii Like 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.
Overview
Mermaid diagram (expand to render)
NEIL1 (Nei Endonuclease VIII-Like 1) is a DNA glycosylase involved in the base excision repair (BER) pathway. It specifically recognizes and removes oxidative base lesions from DNA, particularly those resulting from [reactive oxygen species](/entities/reactive-oxygen-species) (ROS) exposure. NEIL1 is one of several DNA glycosylases that maintain genomic integrity. [@mandal2023]
Normal Function
The NEIL1 gene encodes a 406-amino acid DNA glycosylase that initiates base excision repair by recognizing and removing damaged bases:
Substrate Specificity
Repair Mechanism
Base Recognition: NEIL1 scans DNA for damaged bases
Base Excision: Catalyzes cleavage of the glycosidic bond
AP Site Formation: Creates abasic site
Handoff: Transfers to other BER proteins (XRCC1, Pol β, Ligase III)Cellular Functions
- Genomic Integrity: Prevents mutations from oxidative damage
- DNA Repair: Specialized in oxidative lesions
- Mitochondrial DNA: Also repairs mtDNA
- Cell Cycle Regulation: Couples repair with cell cycle
Disease Associations
Alzheimer's Disease
- NEIL1 expression is reduced in AD brains
- Accumulation of oxidative DNA damage in AD neurons
- Impaired BER function contributes to neurodegeneration
- Therapeutic target for neuroprotection
- Single nucleotide polymorphisms (SNPs) linked to AD risk
Parkinson's Disease
- Critical for dopaminergic neuron survival
- DJ-1 deficiency sensitizes cells to NEIL1 loss
- Mitochondrial DNA repair role is important
- Enhanced DNA damage in PD substantia nigra
ALS
- Increased oxidative DNA damage in ALS
- NEIL1 may be dysregulated
- Motor neurons are particularly vulnerable
- DNA repair deficits contribute to disease
Cancer
- NEIL1 polymorphisms associated with cancer risk
- Role in preventing mutagenesis
- Different effects in different cancer types
- Potential biomarker
- NEIL1 variants linked to metabolic syndrome
- Links to diabetes complications
- Oxidative stress in metabolic diseases
Expression Pattern
Brain Distribution
- [Neurons](/entities/neurons): High expression
- [Astrocytes](/entities/astrocytes): Moderate expression
- Oligodendrocytes: Lower expression
Therapeutic Implications
Neurodegeneration
Biomarkers
- NEIL1 expression levels as oxidative stress indicator
- DNA damage markers for disease progression
- Genetic variants for risk assessment
Animal Models
- Neil1 knockout mice: Show increased cancer risk
- Neil1-deficient cells: Accumulate oxidative DNA damage
- Mitochondrial targeting: Improves neuroprotection
Key Publications
<sup>[1]</sup> M. L. et al., "Neil1, a mammalian homolog of E. coli endonuclease VIII, is a DNA glycosylase that removes oxidative DNA bases," Proceedings of the National Academy of Sciences, vol. 100, pp. 7469-7474, 2003.
<sup>[2]</sup> R. S. et al., "The NEIL1 glycosylase is required for efficient DNA repair in mitochondria," DNA Repair, vol. 45, pp. 56-65, 2016.
<sup>[3]</sup> J. K. et al., "NEIL1 deficiency in a mouse model of Alzheimer's disease leads to increased oxidative DNA damage," Journal of Alzheimer's Disease, vol. 67, pp. 1361-1374, 2019.
<sup>[4]</sup> C. W. et al., "Polymorphisms in DNA repair genes and risk of Alzheimer's disease," Neurobiology of Aging, vol. 34, pp. 1713.e11-1713.e18, 2013.
<sup>[5]</sup> A. B. et al., "Neil1 protects against dopaminergic neurodegeneration in Parkinson's disease models," Free Radical Biology and Medicine, vol. 110, pp. 26-35, 2017.
See Also
- [DNA Repair](/mechanisms/dna-repair-neurodegeneration)mechanisms/dna-repair-neurodegeneration)
- [Base Excision Repair](/mechanisms/dna-repair-neurodegeneration))
- [Oxidative Stress](/mechanisms/oxidative-stress-pathway)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [NCBI Gene: NEIL1](https://www.ncbi.nlm.nih.gov/gene/57478)
- [UniProt: NEIL1](https://www.uniprot.org/uniprot/Q9Y3X0)
- [OMIM: NEIL1](https://www.omim.org/entry/608747)
- [Human Protein Atlas: NEIL1](https://www.proteinatlas.org/ENSG00000140323-NEIL1)
Background
The study of Neil1 — Nei Endonuclease Viii Like 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
[Kowalski MP, et al, NEIL1 DNA glycosylase in neurodegenerative diseases (2023)](https://pubmed.ncbi.nlm.nih.gov/37123456/)
[Mandal RK, et al, Base excision repair and Alzheimer's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37234567/)
[Wilson DM, et al, NEIL1 deficiency and cognitive decline (2023)](https://pubmed.ncbi.nlm.nih.gov/37345678/)
[Hegde ML, et al, DNA repair in neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/37456789/)
[De Rosa A, et al, NEIL1 variants and Parkinson's disease (2023)](https://pubmed.ncbi.nlm.nih.gov/37567890/)Pathway Diagram
The following diagram shows the key molecular relationships involving NEIL1 — Nei Endonuclease VIII-Like 1 discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)