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

Gemici, Yagmur İnalkac and Dundar, Muhammed and Gozukara, Harika Gozde and Koc, Ahmet (2025) Adaptive and terminal endoplasmic reticulum stress genes methylation levels in Parkinson patients’ peripheral blood. IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE, 78 (11-12). pp. 417-423. ISSN 0019-1442

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Abstract

Background and purpose – Misfoldedprotein stress has come to the fore amongthe molecular mechanisms that can causedegeneration. Whereas one of the mostimportant protein of adaptive EndoplasmicReticulum stress (ERS) is XBP1, CHOP andASK proteins are associated with apoptosisand terminal ERS. To the best of our knowledge, methylation levels of adaptive andterminal ERS genes in Parkinson’s Disease(PD) patients’ blood are unknown. We aimedto evaluate if there is a difference in theDNA methylation levels of the ERS relatedprotein-coding genes in peripheral blood ofPD patients compared with healthy controls.The clinical significance of these gene methylation levels was evaluated as the secondaim.Methods – DNA was isolated from theblood of PD patients (n=23) and controls(n=19). We used a methylation-specific qPCRapproach to assess the methylation statusof the ERS genes. The correlation betweenclinical findings and the methylation levels inPD patients were evaluated with appropriatestatistical methods.Results – Terminal ERS related genes werestatistically significantly hypomethylatedin PD (ASK1 p=0.020, and CHOP p<0.001)whereas adaptive ERS gene XBP1’s methylation level was not different between groups.Except for XBP1 and MMSE positive, andCHOP and depression negative correlationno correlation was found between clinical markers and methylation levels of the selected genes. (p=0.040, p=0.024),Conclusion – PD patients’ peripheral bloodmethylation levels of adaptive and terminalERS related genes are significantly differentfrom healthy controls’. While XBP1 is knownto be neuroprotective, CHOP and ASK areimportant proteins in apoptosis, and theirmethylation differences in peripheral bloodprovide a clue that they could be used asbiomarkers in the future. Therefore, furtherbiomarker and treatment studies shouldbe conducted on these proteins and theirpathways.

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