Work

The multifaceted role of ATM protein in neural stem/progenitor cell biology and neurogenesis: beyond DNA damage response

Year: 2026

Type: article

Abstract: The Ataxia Telangiectasia Mutated (ATM) protein kinase is a well recognized master regulator of the DNA damage response (DDR) and cell cycle control whose dysfunction leads to the rare neurological disorder Ataxia Telangiectasia (AT). A mounting body of evidence has revealed unequivocally that ATM relevance extends far beyond its DDR role and includes critical non-canonical functions. This minireview summarizes the current knowledge on ATM role in neural stem progenitor cell (NSPC) biology and in neurogenesis. In particular, herein we highlight how ATM is crucial for NSPC proliferation, differentiation, and survival, acting not only as a guardian of genomic integrity but also as a key orchestrator of developmental timing. Furthermore, we discuss how ATM deficiency in AT leads to dysregulated NSPC proliferation, premature neuronal maturation, and impaired quality control during neurogenesis, potentially contributing to progressive neurodegeneration and complex neurological symptoms associated with this pediatric disorder. By integrating canonical and non-canonical mechanisms, this review may offer a more comprehensive understanding of ATM key role in maintaining brain homeostasis integrity from the stem cell level. Moreover, it adds a more complex perspective on AT pathogenesis and opens novel avenues for future therapeutic interventions.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1751635

Authors: Giulia Boni, Mariagrazia Grilli

Institution: Università degli Studi del Piemonte Orientale “Amedeo Avogadro”

Language: English

Topic: Neurogenesis and neuroplasticity mechanisms

Subfield: Developmental Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801