Investigation of epigenetic changes in molecular pathways involved in the pathogenesis of idiopathic parkinson's disease

Aim: Among the molecular mechanisms of Parkinson's disease pathgenesis misfolded protein stress and autophagy have come to the fore. It was aimed to investigate the role of epigenetic changes that may affect gene expression of proteins involved in endoplasmic reticulum stress and autophagy in the pathophysiology of this disease. Material and Method: DNA was isolated from the blood and the DNAs were cut with methylation specific restriction enzymes. The cut and uncut DNAs were amplified by RT PCR, and the amount of unmethylated DNA was obtained with the difference of the PCR result. The methylation difference between patients and controls and the relationship between patient's inflammation markers were evaluated. Results: The methylation levels of genes were lower in PD patients (EIF2AK3 p=0.015, MAOA p=0.003, ATF6 p=0.002, NBR1 p=0.007, GBA p=0.012, LRRK2 p=0.043, PRKN p=0.005, ASK1 p=0.035 and CHOP p<0.001). XBBP was not statistically significant (p=0.157). A positive correlation was observed between XBP1 and mini mental test (r=0.563, p=0.003), A negative correlation was observed between XBP1 and sedimentation (r=-0.661, p=0.010), PRKN and depression (r=-0.434, p=0.030), CHOP and M/HDL (r=-0.437, p=0.038), LRRK2 and sedimentation (r=-0.546, p=0.043). Conclusion: There is a relationship between ER stress, autophagy and epigenetic regulation in the pathogenesis of PD. This relationship creates the balance between neurodegenerative and neuroprotective pathways. Hypomethylation in terminal ER stress-related genes thought to accelerate the neurodegenerative process. Especially after the development of PD, the bidirectional interaction of hypomethylation and inflammation in these genes is an important factor in the progression of PD clinic.