Computational modeling of ATM signaling: a predictive framework for drug repurposing in ataxia-telangiectasia.

ABSTRACT: Ataxia-Telangiectasia (A-T) is a rare genetic disorder caused by ATM mutations, leading to impaired DNA repair, oxidative stress, and neurodegeneration. We developed a computational model of ATM-mediated signaling using ordinary differential equations in COPASI, capturing key processes including DNA damage sensing, cell cycle regulation, autophagy, and oxidative stress response. The model simulates physiological, ATM-deficient, and drug-treated conditions to explore repurposing strategies. We evaluated the effects of spermidine, omaveloxolone, and HDAC4 inhibition, revealing mechanisms by which these compounds modulate dysfunctional signaling. Sensitivity and stability analyses confirmed the model's robustness, while enrichment analysis validated involvement of key pathways. Our results hi

SUBMITTER: Merulla AE 

PROVIDER: S-EPMC12749466 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature