DNA Damage Repair: A Crucial Link to Neurological Disorders

Environmental stressors and endogenous metabolites constantly threaten DNA integrity; therefore, terrestrial organisms have evolved sophisticated repair and maintenance pathways to eliminate DNA lesions and preserve genome stability. Defective or inefficient DNA repair mechanisms compromise genomic integrity and contribute to the onset and progression of various diseases. In recent years, numerous proteins and signaling pathways essential for DNA damage repair have been extensively characterized. Notably, many of these factors also play critical roles in brain development and are implicated in the pathogenesis of neurological disorders. In this review, we summarize current knowledge on the sources of DNA damage in the nervous system, the major repair pathways operating in neural cells, and the neurological disorders associated with defects in these mechanisms. We also discuss emerging evidence linking DNA repair dysregulation to complex neurodegenerative diseases and highlight key questions that remain to be addressed in this rapidly evolving field.