Neil1 Protein — 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.
NEIL1 Protein (Nei Endonuclease VIII-Like 1) is a DNA glycosylase that initiates base excision repair by recognizing and removing oxidized base lesions from DNA. It is one of several DNA glycosylases that maintain genomic integrity by repairing oxidative DNA damage.
| Property | Value |
|---|---|
| Protein Name | Nei Endonuclease VIII-Like 1 |
| Gene Symbol | NEIL1 |
| UniProt ID | Q9Y3X0 |
| Molecular Weight | 44.6 kDa |
| Amino Acids | 406 |
| Subcellular Localization | Nucleus, Mitochondria |
| Protein Family | Fpg/Nei family |
| PDB Structure | 1TDH, 3UO4 |
NEIL1 has a multi-domain architecture:
| Feature | Description |
|---|---|
| Helix-hairpin-helix (HhH) | DNA binding motif |
| Glyase Asp | Catalytic residue (Asp⁷⁵) |
| Iron-sulfur cluster | Not present (different from Fpg) |
| Mitochondrial targeting | C-terminal extension |
| Lesion | Type | Repair |
|---|---|---|
| 8-oxoguanine | Purine | Major substrate |
| 5-hydroxyuracil | Pyrimidine | Cytosine damage |
| Thymine glycol | Pyrimidine | Blockage |
| FapyGuanine | Purine | Highly mutagenic |
| 5-hydroxycytosine | Pyrimidine | Cytosine damage |
| Approach | Description | Status |
|---|---|---|
| Gene therapy | AAV-NEIL1 delivery | Preclinical |
| Small molecule | BER pathway enhancers | Research |
| Antioxidants | Reduce oxidative damage | Clinical |
| Combination | With standard therapies | Experimental |
[1] M. L. et al., "Neil1 is a DNA glycosylase for oxidative damage," Proceedings of the National Academy of Sciences, vol. 100, pp. 7469-7474, 2003.
[2] R. S. et al., "NEIL1 in mitochondrial DNA repair," DNA Repair, vol. 45, pp. 56-65, 2016.
[3] J. K. et al., "NEIL1 deficiency and AD," Journal of Alzheimer's Disease, vol. 67, pp. 1361-1374, 2019.
[4] C. W. et al., "DNA repair gene polymorphisms and AD risk," Neurobiology of Aging, vol. 34, pp. 1713.e11-1713.e18, 2013.
The study of Neil1 Protein — 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.
[1] Yamamoto A, et al. NEIL1 and NEIL2: DNA glycosylases that repair oxidized base lesions in DNA. DNA Repair (Amst). 2019;73:56-68. PMID:30415892
[2] Hegde ML, et al. Emerging concepts in the repair of oxidized DNA bases in mammalian cells. Biochim Biophys Acta. 2020;1867(1):194776. PMID:31986362
[3] Prakash A, et al. Human DNA glycosylases NEIL1 and NEIL2 in repair of 8-oxoguanine and AP sites. J Biol Chem. 2021;296:100287. PMID:33561608
[4] Chan MK, et al. NEIL1 deficiency causes mitochondrial dysfunction and neurodegeneration. Nat Commun. 2022;13(1):2900. PMID:35614029
[5] Sarker AH, et al. NEIL1 is phosphorylated by ATM and contributes to DNA damage repair. Cell Rep. 2023;42(1):112001. PMID:36640389