Epigenetic mechanisms linking environmental exposure to Parkinson’s disease: a comprehensive review

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction and non-motor symptoms affecting cognition, mood and autonomic function. Both genetic susceptibility and environmental exposures such as pesticides (e.g., paraquat, rotenone), heavy metals (e.g., manganese, lead), tobacco smoke, and caffeine have been implicated in PD pathogenesis. Recent studies highlight the role of epigenetic mechanisms including DNA methylation (e.g., SNCA, PARK2), histone modifications (e.g., H3K9me3, H3K27ac), and microRNAs (e.g., miR-133b, miR-7), in mediating the effects of environmental toxins on neuronal function and survival. These alterations can disrupt transcriptional programs, impair mitochondrial function and promote oxidative stress, neuroinflammation and dopaminergic neuronal loss. Aging further compounds epigenetic dysregulation by reducing chromatin plasticity and enhancing glial reactivity. This review synthesizes current insights into how specific environmental exposures modulate the epigenetic landscape in PD and explores their downstream effects on key pathological processes. We also discuss emerging therapeutic strategies targeting epigenetic modifiers such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and miRNA-based interventions. A clearer understanding of the gene environment epigenome interface may help identify early biomarkers and develop precision medicine approaches for PD.