Fig. 2: Overview of reported links between environmental risk factors of PD and epigenetic mechanisms.
From: Linking environmental risk factors with epigenetic mechanisms in Parkinson’s disease
The pesticide paraquat upregulates α-syn and facilitates colocalisation with histones in mouse nigral neurons. Paraquat also increases acetylation of multiple histone residues in SH-SY5Y cells and rat N27 dopaminergic cells, the latter via inhibition of HDAC. MPP+ (indicated in brackets as it is not strictly an environmental exposure) and rotenone increase acetylation of histones in SH-SY5Y cells, while dieldrin has the same effect in N27 cells as well as SNpc and striatum of mice. The heavy metal manganese increases methylation of CpG sites in SH-SY5Y cells. In human PD cases and SNCA transgenic mice, α-syn sequesters DNMT1 out of the nucleus, thereby reducing total levels of DNA methylation43,96,97,98,99,107.
