New Views of the DNA Repair Protein Ataxia–Telangiectasia Mutated in Central Neurons: Contribution in Synaptic Dysfunctions of Neurodevelopmental and Neurodegenerative Diseases
Articolo
Data di Pubblicazione:
2023
Citazione:
New Views of the DNA Repair Protein Ataxia–Telangiectasia Mutated in Central Neurons: Contribution in Synaptic Dysfunctions of Neurodevelopmental and Neurodegenerative Diseases / S. Briguglio, C. Cambria, E. Albizzati, E. Marcello, G. Provenzano, A. Frasca, F. Antonucci. - In: CELLS. - ISSN 2073-4409. - 12:17(2023 Aug), pp. 2181.1-2181.21. [10.3390/cells12172181]
Abstract:
Ataxia–Telangiectasia Mutated (ATM) is a serine/threonine protein kinase principally
known to orchestrate DNA repair processes upon DNA double-strand breaks (DSBs). Mutations
in the Atm gene lead to Ataxia–Telangiectasia (AT), a recessive disorder characterized by ataxic
movements consequent to cerebellar atrophy or dysfunction, along with immune alterations, ge-
nomic instability, and predisposition to cancer. AT patients show variable phenotypes ranging from
neurologic abnormalities and cognitive impairments to more recently described neuropsychiatric
features pointing to symptoms hardly ascribable to the canonical functions of ATM in DNA damage
response (DDR). Indeed, evidence suggests that cognitive abilities rely on the proper functioning
of DSB machinery and specific synaptic changes in central neurons of ATM-deficient mice unveiled
unexpected roles of ATM at the synapse. Thus, in the present review, upon a brief recall of DNA dam-
age responses, we focus our attention on the role of ATM in neuronal physiology and pathology and
we discuss recent findings showing structural and functional changes in hippocampal and cortical
synapses of AT mouse models. Collectively, a deeper knowledge of ATM-dependent mechanisms in
neurons is necessary not only for a better comprehension of AT neurological phenotypes, but also for
a higher understanding of the pathological mechanisms in neurodevelopmental and degenerative
disorders involving ATM dysfunctions.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ATM; hippocampus; synapse; GABA; glutamate; autism spectrum disorders; Alzheimer’s disease
Elenco autori:
S. Briguglio, C. Cambria, E. Albizzati, E. Marcello, G. Provenzano, A. Frasca, F. Antonucci
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