Adaptive and terminal endoplasmic reticulum stress genes methylation levels in Parkinson patients' peripheral blood.

Abstract

Background and purpose: Misfolded protein stress has come to the fore among the molecular mechanisms that can cause degeneration. Whereas one of the most important protein of adaptive Endoplasmic Reticulum stress (ERS) is XBP1, CHOP and ASK proteins are associated with apoptosis and terminal ERS. To the best of our knowledge, methylation levels of adaptive and terminal ERS genes in Parkinson's Disease (PD) patients' blood are unknown. We aimed to evaluate if there is a difference in the DNA methylation levels of the ERS related protein-coding genes in peripheral blood of PD patients compared with healthy controls. The clinical significance of these gene methylation levels was evaluated as the second aim.

Methods: DNA was isolated from the blood of PD patients (n=23) and controls (n=19). We used a methylation-specific qPCR approach to assess the methylation status of the ERS genes. The correlation between clinical findings and the methylation levels in PD patients were evaluated with appropriate statistical methods.

Results: Terminal ERS related genes were statistically significantly hypomethylated in PD (ASK1 p=0.020, and CHOP p.

Conclusion: PD patients' peripheral blood methylation levels of adaptive and terminal ERS related genes are significantly different from healthy controls'. While XBP1 is known to be neuroprotective, CHOP and ASK are important proteins in apoptosis, and their methylation differences in peripheral blood provide a clue that they could be used as biomarkers in the future. Therefore, further biomarker and treatment studies should be conducted on these proteins and their pathways.