Autophagy response in chronic neuronal oxidative stress

Abstract

AbstractAge‐associated neurodegenerative diseases like Alzheimer's and Parkinson's disease (PD) but also glaucoma is generally accompanied by intracellular stress, malignant accumulations of dysfunctional proteins and a disturbance of the proteostasis. Over time adaptation and increased resilience are measures to make neurons more stable against age‐ and disease‐related challenges. The hippocampal cell line HT22 has been used to illustrate the adaptive ability in response to oxidative stress by enhancing autophagic activity via especially the process of BAG3‐mediated selective macroautophagy.We extended the resistance protocol and generated a novel HT22 cell line that is resistant to thapsigargin, depleting intracellular Ca2+ stores and a potent inducer of ER stressor.We observed a significantly increased LC3B‐II and p62 flux in thapsigargin‐resistant (TgR) compared with HT22‐WT | ells at both, basal and starved conditions. Intriguingly, when looking at the process of ER‐phagy manifold changes are occurring in TgR cells.We suggest that the observed changes in autophagy‐related process, including ER‐phagy, may promote resistance against age‐related Ca2+ disturbance and Ca2+ stress in neuronal cells. Taken together, neuronal cell lines selected for a particular resistance allow molecular insights into neuronal adaptability.