Neurotoxicity of Polycyclic Aromatic Hydrocarbons: ROS-Mediated Mechanisms in Neurodegenerative Diseases

Polycyclic Aromatic Hydrocarbons (PAHs) are pervasive environmental toxicants generated predominantly through incomplete combustion processes. Emerging evidence increasingly implicates PAHs in neurotoxicity and the progression of neurodegenerative diseases. This study synthesizes current mechanistic insights, emphasizing the central role of Reactive Oxygen Species (ROS) in mediating PAH-induced neuronal damage. We present an integrated framework linking PAH metabolic activation to oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and apoptosis. Attention is given to the mechanistic convergence between PAH-induced ROS generation and hallmark pathologies of Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), including amyloid-beta aggregation, tau hyperphosphorylation, and α-synuclein misfolding. Furthermore, this review evaluates the synergistic impact of environmental co-exposures (e.g., particulate matter and heavy metals) and epigenetic modifications in amplifying neurotoxicity. Biomarkers of exposure and early neurodegenerative effects are critically examined to support translational relevance. A conceptual mechanistic model is proposed to unify molecular pathways and disease progression. Finally, therapeutic strategies targeting oxidative stress pathways and policy-level interventions for exposure mitigation are discussed. This work provides a comprehensive, systems-level understanding of PAH neurotoxicity and highlights critical research gaps necessary for advancing environmental neurotoxicology and public health protection.