Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

Figure 4

Schematic representing probable involvement of epigenetic deregulation caused by the overexpression of α-synuclein in in vitro and in in vivo cell models of Parkinson’s disease. The oxidative stress resulting from Mn exposure has a potential to alter epigenetic regulation of α-synuclein via hypomethylation of SNCA gene promoter or through downregulation of miR-7/miR-153. Overexpressed α-synuclein acts epigenetically via sequestration of DNA methyltransferase in cytoplasm. This causes the global change in DNA methylation profile of genes associated with PD. α-Synuclein inside nucleus regulates the expression of PKCδ epigenetically, a proximal regulator of apoptosis. α-Synuclein inhibits binding of protein transcriptional machinery to PKCδ gene promoter region via binding histone protein p300 and inhibiting its histone acetyltransferase activity.