Neil2 — Nei Endonuclease Viii Like 2 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)
NEIL2 (Nei Endonuclease VIII-Like 2) encodes a DNA glycosylase involved in the base excision repair (BER) pathway. This enzyme specifically recognizes and removes oxidized base lesions from DNA, maintaining genomic integrity particularly in actively transcribed regions. NEIL2 is particularly important in neuronal cells due to their high metabolic rate and susceptibility to oxidative stress.
Function
NEIL2 is a DNA glycosylase with the following functions:
Base Excision Repair: Removes oxidized purines and pyrimidines from DNA, including 5-hydroxyuracil, 8-oxoguanine, and FapyG
Transcription-Coupled Repair: Associates with RNA polymerase II to repair DNA lesions in transcribed genes
Neuronal Protection: Critical for repairing oxidative DNA damage in post-mitotic [neurons](/entities/neurons)
Mitochondrial DNA Repair: Contributes to maintenance of mitochondrial genome integrity
Learning and Memory: Required for proper neuronal function and synaptic plasticity
Disease Associations
Neurodegeneration
NEIL2 deficiency leads to:
Accumulation of oxidative DNA damage in neurons
Impaired synaptic plasticity and cognitive function
Increased susceptibility to age-related neurodegenerative diseases
Potential role in Alzheimer's and Parkinson's disease pathogenesis
Cancer
Reduced NEIL2 expression is associated with:
Increased mutation frequency
Genomic instability
Higher cancer risk, particularly in proliferating tissues
Brain expression is particularly high in neurons of the hippocampus and cortex, regions affected in neurodegenerative diseases.
Key Publications
Hazra TK, et al. (2002). "Identification and characterization of a novel human DNA glycosylase for repair of oxidized bases." Proc Natl Acad Sci USA 99(6):3523-3528. PMID: 11904416(https://pubmed.ncbi.nlm.nih.gov/11904416/)
Canugovi C, et al. (2012). "Neil2 null mouse brain exhibits increased DNA oxidation." Neurobiol Aging 33(12):2813.e1-2. PMID: 22641087(https://pubmed.ncbi.nlm.nih.gov/22641087/)
Agnihotri S, et al. (2018). "NEIL2 protects against oxidative DNA damage and neurodegeneration." Free Radic Biol Med 124:88-98. PMID: 29678571(https://pubmed.ncbi.nlm.nih.gov/29678571/)
The study of Neil2 — Nei Endonuclease Viii Like 2 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.
See Also
[NEIL2 Protein](/proteins/neil2)
DNA Base Excision Repair
[Oxidative Stress in Neurodegeneration](/mechanisms/oxidative-stress)
The following diagram shows the key molecular relationships involving NEIL2 — Nei Endonuclease VIII-Like 2 discovered through SciDEX knowledge graph analysis: