In response to diverse stress stimuli, including nutrient restriction, infections or proteotoxicity, eukaryotic cells activate a common adaptive pathway, termed the integrated stress response (ISR), to restore cellular homeostasis. The core event in this pathway is the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) by one of four members of the eIF2α kinase family, which leads to a decrease in global protein synthesis and also the induction of selected genes that together promote cellular recovery. We are focused on understanding the contribution of this signaling pathway to neurodegenerative processes and aging. Using in vivo and in vitro models, we study the consequences of targeting ISR components to open new therapeutic strategies for treating neurodegenerative diseases.