Environmental epigenetic modifiers in neurodegenerative diseases: a systematic review of epigenomic mechanisms and therapeutic targets

Background Environmental contaminants and neurotoxicants are becoming more widely acknowledged as major causes of neurodegenerative illnesses due to systemic biological disruption including oxidative stress, mitochondrial dysfunction, chronic neuroinflammation, and chromatin remodeling–associated epigenetic dysregulation epigenetic modification. According to new research, exposures to heavy metals, gaseous pollutants, particulate matter, and synthetic neurotoxicants alter gene-regulatory networks and accelerate neurodegenerative processes. Objective With an emphasis on molecular mechanisms, developmental neurotoxicity, and translational pathways connecting environmental exposures with epigenomic changes and neurological outcomes, the goal of this systematic review is to compile the most recent data on environmental epigenetic modifiers in neurodegenerative diseases. Method Using structured searches across major biomedical databases, the review was carried out in accordance with PRISMA principles. A multistage selection procedure was used to evaluate studies that addressed environmental neurotoxicants, epigenetic processes (DNA methylation, histone modification, and non-coding RNAs), and neurodegenerative consequences. To find common routes and life-course exposure effects, relevant experimental, epidemiological, mechanistic, and translational data were qualitatively summarized. Results The findings of the included research show that exposure to the environment causes oxidative stress, mitochondrial dysfunction, neuroinflammation, and chromatin remodeling. These effects result in alterations in histone acetylation, DNA methylation patterns, and dysregulated expression of microRNAs. Amyloidogenic signaling, synaptic dysfunction, and neuronal death were consistently linked to both chemical and particulate matter neurotoxicants. Furthermore, early environmental stressors create long-term epigenetic programming that heightens vulnerability to eventual neurodegenerative pathology, according to developmental exposure models. Conclusion An important link between the exposome and the risk of neurodegenerative diseases is represented by environmental epigenetic modifiers. Epigenetic pathways including histone acetylation imbalance, microRNA-mediated regulation (e.g., miR-574-5p), and DNA methylation changes emerge as potential biomarkers and therapeutic targets. Future research should prioritizemulti-omics techniques, harmonized exposure assessment, and longitudinal human investigations to advance precision prevention and intervention strategies.