Genetic lesions that compromise the ribosome P-stalk implicate direct signalling from the ribosome to the translation initiation factor eIF2 kinase GCN2 in the cellular response to amino acid starvation.
Vanishing White Matter Disease mutations compromise the function of the essential translation initiation factor eIF2B by destabilizing the holoenzyme, and the small molecule ISRIB reverses their pathogenic effect by promoting complex formation.
Activation of the integrated stress response by stalled translation elongation complexes attenuates neurodegeneration, and demonstrates a protective link between a decrease in the rate of translation initiation and defects in translation elongation.
Directly targeting the ribosome to attenuate translation partly mimics the integrated stress response, increasing lifespan and preserving protein folding capacity even in older individuals with dysfunctional stress response signaling.
A survey of researchers at the Montreal Neurological Institute and Hospital provides insights into the challenges and opportunities involved in adopting an open science policy across an entire patient-oriented academic institution.