ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry
Abstract
:1. Introduction
ATM Protein
2. ATM Governs Genomic Integrity
2.1. ATM Mediates DDR
2.2. ATM Regulates Cell Cycle and Apoptosis
2.3. ATM and Cancer Susceptibility
3. Multiple Roles of ATM Protein Kinase: Beyond the DNA Damage Response
3.1. ATM Functions in Oxidative Stress
3.2. Role of ATM in Insulin Signalling Pathways
3.3. ATM Mediates Epigenetic Regulation
3.4. ATM and Neuronal Function: Implication in Synaptic Vesicles’ Behaviour in Neurons
3.5. ATM and Neuronal Function: Implication in GABAergic Development and Excitatory/Inhibitory Equilibrium
4. ATM Dysregulation in Neurological Diseases
4.1. ATM Involvement in Neurodegenerative Disorders and Brain Senescence
4.2. ATM Involvement in Cognition
5. Conclusions and Future Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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References | Experimental Models | ATM Levels | Changes |
---|---|---|---|
Petersen et al. [151] | • Drosophila mutant for ATM | Low | • Neuron and glial cell death in the adult brain • High inflammation • Reduction in mobility and longevity |
Shen et al. [152] | • R1.40, PS/APP, 3xTg mouse models of AD • Human AD brains | Low | • Nuclear translocation ofhistone deacetylase 4 • Trimethylation of histone H3 • The presence of cell cycle activity • Low ATM signaling in neurons in regions where degeneration is prevalent |
Illuzzi et al. [153] Giuliano et al. [154] | • Cells transfected with mHTT | High (activation) | • Elevated DNA damage and oxidative stress |
Lu et al. [155] | • BACHA mouse model of HD • Human HD brain | High | Reducing Atm ameliorates: • mHTT fragment toxicity in cells • spontaneous locomotion, motor coordination, depressive-like behaviours |
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Pizzamiglio, L.; Focchi, E.; Antonucci, F. ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry. Cells 2020, 9, 1969. https://doi.org/10.3390/cells9091969
Pizzamiglio L, Focchi E, Antonucci F. ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry. Cells. 2020; 9(9):1969. https://doi.org/10.3390/cells9091969
Chicago/Turabian StylePizzamiglio, Lara, Elisa Focchi, and Flavia Antonucci. 2020. "ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry" Cells 9, no. 9: 1969. https://doi.org/10.3390/cells9091969