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• W2912998668 abstract "Significance The integrated stress response (ISR) protects cells from a variety of harmful stressors by temporarily halting protein synthesis. However, chronic ISR activation has pathological consequences and is linked to several neurological disorders. Pharmacological inhibition of chronic ISR activity emerges as a powerful strategy to treat ISR-mediated neurodegeneration but is typically linked to adverse effects due to the ISR’s importance for normal cellular function. Paradoxically, the small-molecule ISR inhibitor ISRIB has promising therapeutic potential in vivo without overt side effects. We demonstrate here that ISRIB inhibits low-level ISR activity, but does not affect strong ISR signaling. We thereby provide a plausible mechanism of how ISRIB counteracts toxic chronic ISR activity, without disturbing the cytoprotective effects of a strong acute ISR." @default.
• W2912998668 created "2019-02-21" @default.
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• W2912998668 date "2019-01-23" @default.
• W2912998668 modified "2023-10-14" @default.
• W2912998668 title "Small molecule ISRIB suppresses the integrated stress response within a defined window of activation" @default.
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• W2912998668 doi "https://doi.org/10.1073/pnas.1815767116" @default.
• W2912998668 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6369741" @default.
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• W2912998668 hasPublicationYear "2019" @default.
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