Epigenomic alterations in Parkinson´s disease

Certain toxins enter the neuronal cells and cause histone modifications that alter gene expression. In the nucleus, aSyn interacts with H1 forming a complex and also with H3 inhibiting its acetylation. In turn, histones trigger the aggregation of aSyn. Some of the genes affected are: PARK16, GPNMB, STX1B, due to aberrant DNA methylation. Additionally, miR-205 is able to suppress the expression of LRRK2 protein by binding to its 3′ UTR mRNA region. Conversely, mutant LRRK2 inhibits let-7 and miR-184* which participate in cell survival. Overexpression of miR-494 reduces the levels of PARK7. Furthermore, several miRNAs bind to snca mRNA sequence and prevent its translation. Finally, mutant aSyn is thought to affect the production of certain miRNAs (1).

Reference

1. Pavlou M, Outeiro T. Epigenetics in Parkinson’s Disease. Advances in Experimental Medicine and Biology. 2017;:363-390.

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