Ionizing Radiation as a Factor in Neurodegeneration: Current Insights into Pathogenesis and Consequences

Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, which are accompanied by neurocognitive, sensory, and motor impairments, significantly reduce the quality of life of patients worldwide. According to statistics, 50%–90% of patients undergoing radiation therapy for brain tumors develop cognitive impairment. One of the factors contributing to brain cell damage is ionizing radiation. It is well established that radiation induces direct effects, including deoxyribonucleic acid strand breaks, and indirect effects mediated by the accumulation of adenosine-5'-triphosphate, which in turn promotes oxidative stress, mitochondrial dysfunction, and inflammation. These processes can cause a violation of the integrity of cellular structures and the activation of the body’s defense mechanisms. This article discusses the effect of ionizing radiation on the development of oxidative stress, impaired antioxidant protection, lipid peroxidation, as well as the induction of ferroptosis, inflammation, and pyroptosis. The relevant molecular mechanisms of these processes are also discussed. Overall, this review highlights that radiation-induced brain cell damage may contribute to the development of various neurological and neuropsychological disorders. Thus, therapeutic approaches aimed at reducing radiation-induced oxidative stress and neuroinflammation represent a promising strategy for preventing radiation-induced brain injury and related disorders.