Dissecting the cell biology of the ISR in cognitive disorders at the single-cell resolution

Abstract

The integrated stress response (ISR) is widely recognized as a fundamental cellular mechanism that maintains homeo - stasis by regulating protein synthesis in response to both intracellular and extracellular stress (1). The ISR also repre - sents a major frontier in brain health and cognitive function. It dynamically regulates the synaptic processes that are required to form a long - term memory (1, 2 ). Moreover, per - sistent ISR activation drives neuronal dysfunction and con - tributes to the pathogenesis and cognitive decline across a wide range of neurodegenerative and neurodevelopmental disorders (1). Despite these advances, the specific cellular mechanisms by which sustained ISR activation impairs cog - nitive function remain largely unknown. The study by Torkenczy