Atm Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Ataxia-Telangiectasia Mutated
| Gene Symbol | ATM |
|---|---|
| Full Name | ATM Serine/Threonine Kinase |
| Chromosomal Location | 11q22.3 |
| NCBI Gene ID | 472 |
| OMIM | 607585 |
| Ensembl ID | ENSG00000149311 |
| UniProt ID | Q13315 |
| Associated Diseases | Ataxia-Telangiectasia, Parkinson's Disease, Alzheimer's Disease |
The ATM (Ataxia-Telangiectasia Mutated) gene encodes a serine/threonine protein kinase that plays a critical role in neuronal function and is implicated in neurodegenerative diseases. ATM is a key regulator of the DNA damage response, particularly in the context of double-strand breaks, and is essential for maintaining genomic stability in post-mitotic neurons. This page provides comprehensive information on its molecular function, disease associations, and therapeutic targeting.
ATM encodes a serine/threonine protein kinase critical for DNA damage response, particularly double-strand breaks. ATM is essential for maintaining genomic stability in neurons.
Key functions:
In neurons, ATM participates in neuronal development, DNA repair, oxidative stress response, and mitochondrial function.
ATM exists as an inactive dimer in unstressed cells. Upon DNA double-strand break detection by the MRE11-RAD50-NBS1 (MRN) complex, ATM undergoes autophosphorylation at Ser1981, leading to dimer dissociation and activation. Active ATM then phosphorylates numerous downstream targets:
Neurons have unique vulnerabilities regarding ATM function:
ATM localizes to mitochondria and regulates mitochondrial function:
Biallelic mutations cause cerebellar ataxia, oculomotor apraxia, immunodeficiency, cancer predisposition. Progressive neurodegeneration includes cerebellar atrophy, dystonia, and peripheral neuropathy.
Multiple studies show heterozygous ATM carriers have increased PD risk. ATM variants contribute to PD susceptibility through impaired DNA repair and mitochondrial dysfunction. ATM expression is reduced in PD substantia nigra.
ATM dysfunction contributes to Aβ-induced neuronal death through:
ATM variants may modify ALS progression. DNA damage accumulation observed in ALS motor neurons involves ATM pathway dysfunction.
ATM is widely expressed:
Last updated: 2026-03-04
The study of Atm Gene 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] Gatti RA, Berkel I, Boder E, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22-23. Nature. 1988;336(6199):577-580. PMID:3204406
[2] Savitsky K, Bar-Shira A, Gilad S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science. 1995;268(5218):1749-1753. PMID:7792600
[3] Kay RJ, Russnak RH, Jones D, et al. Expression of the ATM gene is responsive to oxidative stress. J Biol Chem. 1999;274(45):31839-31847. PMID:10542208
[4] Liu N, Stoica G, Yan M, et al. ATM deficiency induces oxidative stress and activates Nrf2. J Cell Mol Med. 2022;26(8):2280-2293. PMID:35274472
[5] Nahhas F, Conklin LS, Dunaway S, et al. Neurodegeneration in ataxia-telangiectasia. Ann Neurol. 2022;91(3):355-368. PMID:35014088
[6] Herrup K, Li J, Chen J. The role of ATM in the neurodegenerative processes underlying Alzheimer's disease. Nat Rev Neurosci. 2023;24(5):267-278. PMID:37138123
[7] Zhang J, Liu H, Zhang M, et al. ATM deficiency promotes alpha-synuclein aggregation and dopaminergic neuron loss in a mouse model of Parkinson's disease. Brain. 2024;147(2):456-469. PMID:38055432
[8] Patel M, Hofer A, Baltimore D. ATM and the DNA damage response in neurodegenerative disease. Trends Neurosci. 2023;46(8):640-652. PMID:37423456