Hypothetical model linking gene and environmental factors to transcriptional disregulation of neurogenesis-related genes . Maneb and Paraquat trigger ROS production (1), nitrosylation of transcription factors (2), and missfolding and aggregation of proteins, like α-synuclein. Lewy body formation in association with α-synuclein aggregation and phosphorylated-Tau accumulation in the context of LRRK2 mutations might contribute to misslocalization of Fox proteins (3) or aberrant phosphorylation triggering apoptosis and neuronal death (4). Alpha-synuclein can directly bind DNA and also alter DNA methylation (5). The combination of these factors will impact on the transcription of Fox-regulated neurogenesis-related genes (6).