Neuroprotection by a secreted component of the cellular stress response

PROJECT NARRATIVE The integrative stress response is an evolutionary conserved pathway to allows cells to react to various stress stimuli to restore cellular homeostasis. We found that the activation of this process in neurons leads to the secretion of a protein fragment that enhances the resilience of surrounding cells to cell stress. We propose to study how this signaling molecule is generated and secreted from neurons in response to stress, how it affects recipient neurons, and how its activity is coordinated with transcriptional programs to facilitate cell survival.