Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress

• DOI: 10.1016/j.redox.2023.102943
• Publication Date: 2023-10-20T08:53:54Z
• Authors: Thu Nguyen Minh Pham; Natarajan Perumal; Caroline Manicam; Marion Basoglu; Stefan Eimer; Dominik C. Fuhrmann; Claus U. Pietrzik; Albrecht M. Clement; Hagen Körschgen; Jana Schepers; Christian Behl
• Keywords: Tunicamycin; ATF6; Thapsigargin

Accumulation of misfolded proteins or perturbation calcium homeostasis leads to endoplasmic reticulum (ER) stress and is linked the pathogenesis neurodegenerative diseases. Hence, understanding ability neuronal cells cope with chronic ER fundamental interest. Interestingly, several brain areas uphold functions that enable them resist challenges associated neurodegeneration. Here, we established novel clonal mouse hippocampal (HT22) cell lines are resistant prolonged (chronic) induced by thapsigargin (TgR) tunicamycin (TmR) as in vitro models study adaption stress. Morphologically, observed a significant increase vesicular und autophagosomal structures both 'giant lysosomes', especially striking TgR cells. While autophagic activity increased under stress, lysosomal function appeared slightly impaired; lines, enhanced ER-phagy. However, proteomic analyses revealed various protein clusters signaling pathways were differentially regulated versus TmR response Additionally, bioenergetic showed shift toward aerobic glycolysis ('Warburg effect') defective complex I oxidative phosphorylation (OXPHOS) machinery. Furthermore, stress-resistant activated unfolded (UPR) comprising IRE1α ATF6 pathways. These findings display wide portfolio adaptive responses could be basis uncover molecular modulators adaptation, resistance, neuroprotection potential pharmacological targets for preventing