2020/04/24 by Mauro Costa‐Mattioli, Peter Walter · 21 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Endoplasmic Reticulum Stress and Disease #Genetics, Aging, and Longevity in Model Organisms #Sirtuins and Resveratrol in Medicine
paper · doi:10.1126/science.aat5314
openalex publication_date 2020/04/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Protein quality control is essential for the proper function of cells and the organisms that they make up. The resulting loss of proteostasis, the processes by which the health of the cell's proteins is monitored and maintained at homeostasis, is associated with a wide range of age-related human diseases. Here, we highlight how the integrated stress response (ISR), a central signaling network that responds to proteostasis defects by tuning protein synthesis rates, impedes the formation of long-term memory. In addition, we address how dysregulated ISR signaling contributes to the pathogenesis of complex diseases, including cognitive disorders, neurodegeneration, cancer, diabetes, and metabolic disorders. The development of tools through which the ISR can be modulated promises to uncover new avenues to diminish pathologies resulting from it for clinical benefit.