N-METHYL-4-PHENYLPYRİDİNİUM IODİDE (MPP+) ARACILI PARKİNSON HÜCRE MODELİNDE OTOFAJİ AKTİVATÖRÜ FLUSPİRİLENİN ENDOPLAZMA RETİKULUMU STRESİNDEKİ IRE1 YOLAĞINA ETKİSİNİN ARAŞTIRILMASI

Abstract

Tureli Ayan Merve, Investigation of the Effect of the Autophagy Activator Fluspirylene on the Ire1 Pathway in Endoplasmic Reticulum Stress in N-Methyl- 4-Phenylpyridinium Iodide (Mpp+) Mediated Parkinson's Cell Model, Hacettepe University Faculty of Medicine Department of Histology and Embryology Residency Thesis, Ankara, 2024. Parkinson's disease, the second most common neurodegenerative disease worldwide, has many underlying molecular mechanisms. One of these mechanisms is endoplasmic reticulum stress. Endoplasmic reticulum stress is detected by three proteins acting as sensors, activating pathways associated with synthesis or degradation in the endoplasmic reticulum. Another molecular mechanism observed in Parkinson's disease is impaired autophagy. Autophagy not only serves as a cellular death mechanism but also plays a salvaging role by clearing damaged organelles and misfolded proteins in the cell. In this study, we aimed to observe and describe the effect of Fluspirilene, which induces ATG5-mediated autophagy, on IRE1, one of the endoplasmic reticulum stress sensors, in a Parkinson's disease model created with MPP+ toxin on H4 human neuroglioma cells. We determined the effect of autophagy on cell viability in the Parkinson's disease model by using the MTT assay. The reversal of impaired autophagy with ATG5-mediated autophagy activation is detected by LC3B immunocytochemistry. By the pIRE1 immunocytochemistry used to detect the endoplasmic reticulum stress, after the standardization of pIRE1 immunoreactivity with the total IRE1 levels measured using the ELISA method, endoplasmic reticulum stress was found to be increased. With the ER-Tracker staining it is seen that the morphology of the endoplasmic reticulum was destroyed in the Parkinson's disease model, but restored with autophagy. With this study, in the MPP+ toxin-mediated Parkinson's disease model the relationship between ATG5-mediated autophagy and IRE1 mediated endoplasmic reticulum stress was shown for the first time