27 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

    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. 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

    eIF2B conformation and assembly state regulate the integrated stress response

    Michael Schoof et al.
    eIF2-P activates the integrated stress response by inducing a conformational change in eIF2B that decreases substrate (eIF2) binding and reduces eIF2B's catalytic activity.
    1. Cell Biology
    2. Neuroscience

    Pharmacological brake-release of mRNA translation enhances cognitive memory

    Carmela Sidrauski et al.
    A compound that prevents stressors such as UV light and viral infection from downregulating protein synthesis inside cells improves memory performance in mice.
    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. Neuroscience

    Small molecule cognitive enhancer reverses age-related memory decline in mice

    Karen Krukowski et al.
    Inhibition of the integrated stress response restores neuronal and immune dysfunction and alleviates memory deficits in aged mice.
    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.
    1. Cell Biology

    Translation in amino-acid-poor environments is limited by tRNAGln charging

    Natalya N Pavlova et al.
    Amino acid limitation triggers preferential uncharging of glutamine-specific tRNAs and depletes polyglutamine tract-containing proteins from mammalian cells, revealing a potential role for polyglutamine tracts as sensors of glutamine sufficiency.
    1. Neuroscience

    Translational control of auditory imprinting and structural plasticity by eIF2α

    Gervasio Batista et al.
    Behavioral pharmacology and molecular biology reveal a translational control mechanism underlying auditory imprinting and structural plasticity that can be pharmacologically manipulated to reopen the critical period.

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