RNA editing in Parkinson's disease: emerging mechanisms, translational potential, and current challenges.

Parkinson's disease (PD) is a major neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and accumulation of α-synuclein. Current treatments primarily focus on symptom alleviation, highlighting the necessity for identifying novel molecular therapeutic targets. RNA editing, as a post-transcriptional process that modifies RNA sequences without altering genomic DNA, is increasingly recognized as an important contributor to the neuronal development and synaptic regulation. Among known RNA editing types, ADAR-mediated adenine-to-inosine (A-to-I) editing is the predominant form in the brain. Accumulating evidence suggests that RNA editing patterns undergo significant alterations in PD patients. This review synthesizes current evidence within a three-layer framework: (1) evidence for RNA editing dysregulation in PD, emphasizing tissue-specific and context-dependent patterns; (2) downstream mechanistic pathways stratified by evidence strength; and (3) experimental models, translational applications, and limitations. A distinction between what is known versus what remains speculative is emphasized throughout. RNA editing changes in PD appear heterogeneous and context-dependent, with brain and peripheral blood showing distinct patterns. Whether editing changes represent disease drivers, compensatory responses, or downstream phenomena remains largely unresolved.