Inhibition of the PERK-Dependent Unfolded Protein Response Signaling Pathway Involved in the Pathogenesis of Alzheimer's Disease

Current Alzheimer Research
Wioletta RozpędekIreneusz Majsterek

Abstract

There is a body of evidence that neurodegenerative disease entities are directly correlated with the perturbations on the molecular level. Hence, the ER stress-mediated Unfolded Protein Response (UPR) is activated resulting in PERK-dependent phosphorylation of the Eukaryotic initiation factor 2 (eIF2α). Thus, the levels of ATF4 and CHOP proteins are significantly increased, which subsequently switches the pro-adaptive branch of the UPR into the pro-apoptotic directly leading to neuronal loss and initiation of the neurodegenerative process. The aim of the presented study was the evaluation of the biological activity of highly specific, small-molecule inhibitors of the PERKdependent UPR signaling pathway. The study was conducted on rat astrocytic DI TNC1 cell line. The level of p-eIF2α was measured by Western blot technique, the cytotoxicity of the investigated compound was assessed by the MTT assay and using the FITC-conjugated Annexin V (Annexin V-FITC) to indicate apoptosis and propidium iodide (PI) to indicate necrosis. The effect of tested compound on cell cycle progression was measured by flow cytometry, where the PI-labelled nuclei were analysed for DNA content. As a result one of the investigated compound LDN-0060609 trig...Continue Reading

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Citations

Mar 25, 2020·International Journal of Molecular Sciences·Wioletta Rozpędek-KamińskaIreneusz Majsterek
Jun 18, 2020·International Journal of Molecular Sciences·Wioletta Rozpędek-KamińskaIreneusz Majsterek
May 1, 2021·International Journal of Molecular Sciences·Wioletta Rozpędek-KamińskaIreneusz Majsterek

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