Epigenetic Regulation in Parkinson’s Disease: Cutting -Edge Insights into miRNAs, lncRNAs and Chromatin Modifiers
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss and abnormal aggregation of α-synuclein. While genetic mutations contribute to disease susceptibility, accumulating evidence highlights the pivotal role of epigenetic regulation in modulating gene expression and disease progression. The epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA-mediated regulation, dynamically influence neuronal function, neuroinflammation, mitochondrial homeostasis, and protein aggregation in Parkinson’s disease. Recent studies have revealed that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are critical regulators of α-synuclein expression, dopaminergic neuron survival, and inflammatory signaling pathways. In parallel, chromatin modifiers such as histone acetyltransferases and deacetylases orchestrate transcriptional programs that determine neuronal vulnerability and resilience. The intricate crosstalk among miRNAs, lncRNAs, and chromatin-modifying complexes underscores the complexity of epigenetic networks in PD pathogenesis. Furthermore, epigenetic alterations have emerged as promising biomarkers for early diagnosis and disease monitoring, as well as attractive therapeutic targets for disease-modifying interventions. Advances in epigenetic-based therapies, including histone deacetylase inhibitors and RNA-based strategies, offer new opportunities for precision medicine in Parkinson’s disease. This review critically summarizes current insights into the roles of miRNAs, lncRNAs, and chromatin modifiers in Parkinson’s disease, discusses their potential as biomarkers and therapeutic targets, and highlights key challenges and future perspectives in translating epigenetic discoveries into clinical applications.