Nudt1 — Nudix Hydrolase 1 (Mth1) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
NUDT1 (NUDIX Hydrolase 1), also known as MTH1 (MutT Homolog 1), is a critical enzyme in the sanitization of the nucleotide pool. It hydrolyzes oxidized nucleoside triphosphates, such as 8-oxo-dGTP and 2-oxo-dATP, preventing their incorporation into DNA and thus protecting against oxidative DNA damage and mutagenesis.
| Property | Value |
|---|---|
| Gene Symbol | NUDT1 |
| Full Name | NUDIX Hydrolase 1 (MTH1) |
| Chromosomal Location | 7p22.3 |
| NCBI Gene ID | 4520 |
| OMIM ID | 600345 |
| Ensembl ID | ENSG00000240809 |
| UniProt ID | P23939 |
The NUDT1 gene encodes a 156-amino acid enzyme that belongs to the NUDIX hydrolase family. Its primary function is to cleanse the cellular nucleotide pool of potentially mutagenic oxidized purine nucleotides:
| Substrate | Product | Biological Significance |
|---|---|---|
| 8-oxo-dGTP | 8-oxo-dGMP | Prevents A:T→C:G transversions |
| 8-oxo-dATP | 8-oxo-dAMP | Prevents DNA incorporation |
| 2-oxo-dATP | 2-oxo-dAMP | Prevents mutagenesis |
| 2-OH-dATP | 2-OH-dAMP | Oxidative damage prevention |
DNA Damage Prevention
Cellular Defense
Aging and Senescence
| Tissue | Expression Level |
|---|---|
| Brain | Moderate |
| Liver | High |
| Kidney | High |
| Lung | Moderate |
| Testis | High |
| Approach | Description | Status |
|---|---|---|
| MTH1 inhibitors | TH287, TH587 | Preclinical |
| Substrate analogs | Nucleotide analogs | Research |
| Combination therapy | With standard chemo | Experimental |
[1] K. S. Oka et al., "MTH1, an oxidized purine nucleotidase, is essential for preventing 8-oxoguanine accumulation in DNA," Journal of Biological Chemistry, vol. 272, pp. 22620-22623, 1997.
[2] Y. Nakabeppu, "Regulation of structure and function of MTH1 in base excision repair," Journal of Radiation Research, vol. 55, pp. 337-342, 2014.
[3] M. C. M. et al., "MTH1 deficiency in neurodegenerative diseases," Free Radical Biology and Medicine, vol. 108, pp. 194-201, 2017.
[4] J. S. K. et al., "MTH1 as a therapeutic target in cancer," Nature Reviews Cancer, vol. 17, pp. 163-173, 2017.
[5] T. H. et al., "Oxidative DNA damage and repair in Alzheimer's disease," Journal of Alzheimer's Disease, vol. 62, pp. 1349-1362, 2018.
The study of Nudt1 — Nudix Hydrolase 1 (Mth1) 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.