Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome

In this study, we found that the integrated stress response (ISR)—a signaling network that maintains proteostasis—was activated in the brains of DS mice and individuals with DS, reprogramming translation. Genetic and pharmacological suppression of the ISR, by inhibiting the ISR-inducing double-stranded RNA–activated protein kinase or boosting the function of the eukaryotic translation initiation factor eIF2-eIF2B complex, reversed the changes in translation and inhibitory synaptic transmission and rescued the synaptic plasticity and long-term memory deficits in DS mice. Thus, the ISR plays a crucial role in DS, which suggests that tuning of the ISR may provide a promising therapeutic intervention.

Source: ScienceNOW - November 13, 2019 Category: Science Authors: Zhu, P. J., Khatiwada, S., Cui, Y., Reineke, L. C., Dooling, S. W., Kim, J. J., Li, W., Walter, P., Costa-Mattioli, M. Tags: Cell Biology, Neuroscience r-articles Source Type: news