ATM Kinase Small Molecule Inhibitors Prevent Radiation-Induced Apoptosis of Mouse Neurons In Vivo.

ABSTRACT: ATM kinase is becoming an important therapeutic target for tumor radiosensitization. Radiation is known to cause neuro-inflammation and neurodegeneration; however, the effects of small molecule ATM inhibitors (ATMi's) and radiation on normal tissue, including healthy brain, are largely unexplored. Therefore, we examined the mouse CNS after ATMi radiosensitization with a focus on the fate of neurons. We used several approaches to assess the effects on the DNA damage response (DDR) and apoptosis of neurons using immunostaining. In vivo, a significant decrease in viable neurons and increase in degenerating neurons and apoptosis was observed in mice treated with radiation alone. On the other hand, an ATMi alone had little to no effect on neuron viability and did not induce apoptosis. Important

SUBMITTER: Aydar Y 

PROVIDER: S-EPMC11981642 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature