Epigenetic Dysregulation of Dopaminergic Neuron Differentiation as a Mechanism of Parkinson’s Disease Development: Translational Perspectives

Abstract

Parkinson's disease is traditionally characterized as a progressive neurodegenerative disorder defined by the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological accumulation of α-synuclein. Although genetic mutations and environmental factors contribute to disease susceptibility, accumulating evidence suggests that epigenetic dysregulation plays a key role both in neuronal differentiation and in later neuronal vulnerability. This review synthesizes current evidence on the mechanisms of epigenetic regulation of dopaminergic neuron differentiation and analyzes how disturbances in DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA networks contribute to the pathogenesis of Parkinson’s disease. Special emphasis is placed on translational implications, including induced pluripotent stem cell (iPSC) modeling, epigenetic biomarkers, and emerging therapeutic strategies aimed at epigenome editing.