Introduction:
Endoplasmic reticulum (ER) stress induced the mobilization of two protein
breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated
degradation, unfolded ER proteins are translocated to the cytosol where they are
cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the
ER capacity, autophagy can be activated in order to undertake the degradative machinery and to
attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles
are included in autophagosomes and delivered to lysosomes for degradation and recycling
of bioenergetics substrate.
Materials and Methods:
Autophagy upon ER stress serves initially as a protective mechanism,
however when the stress is more pronounced the autophagic response will trigger cell death. Because
autophagy could function as a double edged sword in cell viability, we examined the effects
autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal
cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and
autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons.
We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability.
Results and Conclusion:
Based on our findings, we conclude that under ER-stress conditions, inhibition
of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be
neuroprotective.
Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration
