The role of neddylation in mediating radiation-induced neuronal DNA damage and neuroinflammation: Implications for neurodegenerative diseases

Abstract

Neddylation is a post-translational modification that regulates multiple cellular processes, including DNA damage responses and inflammatory signaling. Dysregulation of these pathways has been implicated in neuronal dysfunction and neurodegeneration. This review summarizes current evidence from the literature regarding the role of neddylation in modulating neuronal responses to ionizing radiation–induced DNA damage, with a focus on mechanisms relevant to genomic instability and neuroinflammation. We reviewed experimental and mechanistic studies investigating neddylation-regulated DNA damage repair, telomere integrity, mitochondrial function, and inflammatory signaling in neuronal and neural-related models, particularly in the context of ionizing radiation exposure. Evidence from the literature indicates that neddylation influences key components of the DNA damage response, including repair pathway choice, telomere stability, and mitochondrial homeostasis, as well as inflammatory signaling cascades. Ionizing radiation serves as an experimental paradigm to investigate these processes under conditions of acute genomic stress. While ionizing radiation does not recapitulate the full complexity of neurodegenerative diseases, radiation-based models provide mechanistic insight into neddylation-regulated pathways that may contribute to neuronal dysfunction. The potential relevance of these mechanisms to Alzheimer's disease and other neurodegenerative disorders warrants cautious interpretation and further investigation.