Physical activity and lncRNA-mediated regulation in Parkinson's disease: Mechanistic insights and translational perspectives.

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation contributing to motor and non-motor impairment. Beyond pharmacological management, structured physical activity has been associated with biological adaptations relevant to these processes, including modulation of neurotrophic signaling, mitochondrial function, and inflammatory pathways. Emerging evidence suggests that long noncoding RNAs (lncRNAs) participate in these responses through transcriptional and epigenetic regulation, although current findings remain heterogeneous and largely derived from preclinical models. Limited human data indicate potential associations, but their clinical relevance is not yet established. This review synthesizes current evidence linking physical activity to lncRNA-associated mechanisms in PD, with emphasis on mitochondrial regulation, neuroinflammation, and synaptic function. Key translational considerations and methodological limitations are discussed, highlighting the need for mechanistically grounded human studies.