16 results found
    1. Cell Biology
    2. Neuroscience

    The small molecule ISRIB reverses the effects of eIF2α phosphorylation on translation and stress granule assembly

    Carmela Sidrauski et al.
    Building on previous work which showed that the small molecule ISRIB potently blocks the integrated stress response (Sidrauski et al., 2013), we report on ISRIB's remarkable specificity and fast action in vivo, underscoring its proposed direct effect on translation.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The small molecule ISRIB rescues the stability and activity of Vanishing White Matter Disease eIF2B mutant complexes

    Yao Liang Wong et al.
    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.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski et al.
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Developmental Biology

    Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia

    Cheng Wang et al.
    Integrated stress response-induced expression of ATF4 and its transactivation of SOX9 causes aberrant chondrocyte differentiation and skeletal defects which can be alleviated by modulating initiation-factor eIF2α phosphorylation translation control.
    1. Cell Biology
    2. Neuroscience

    Cell Biology: Less translational control, more memory

    Graham D Pavitt
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    1. Neuroscience

    eIF2α-mediated translational control regulates the persistence of cocaine-induced LTP in midbrain dopamine neurons

    Andon N Placzek et al.
    Building on previous work (Huang et al., 2016), we show that translational control by p-eIF2α is a defense mechanism that prevents persistent cocaine-induced synaptic synaptic potentiation underlying compulsive drug seeking.
    1. Neuroscience

    Translational control by eIF2α phosphorylation regulates vulnerability to the synaptic and behavioral effects of cocaine

    Wei Huang et al.
    Vulnerability to cocaine addiction during adolescence depends on translational control.
    1. Biochemistry and Chemical Biology

    Translation attenuation by minocycline enhances longevity and proteostasis in old post-stress-responsive organisms

    Gregory M Solis et al.
    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.
    1. Cell Biology

    Chronic optogenetic induction of stress granules is cytotoxic and reveals the evolution of ALS-FTD pathology

    Peipei Zhang et al.
    OptoGranules reveal the function of G3BP1 as a stress granule scaffold and demonstrate that protracted stress granule assembly is sufficient to drive neurodegeneration and the evolution of ALS-FTD pathology.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    eIF2B activator prevents neurological defects caused by a chronic integrated stress response

    Yao Liang Wong et al.
    Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.

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