Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury
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- Austin Chou
- Brain and Spinal Injury Center, University of California, San Francisco, CA 94143;
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- Karen Krukowski
- Brain and Spinal Injury Center, University of California, San Francisco, CA 94143;
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- Timothy Jopson
- Brain and Spinal Injury Center, University of California, San Francisco, CA 94143;
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- Ping Jun Zhu
- Department of Neuroscience, Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030;
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- Mauro Costa-Mattioli
- Department of Neuroscience, Memory and Brain Research Center, Baylor College of Medicine, Houston, TX 77030;
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- Peter Walter
- Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143;
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- Susanna Rosi
- Brain and Spinal Injury Center, University of California, San Francisco, CA 94143;
説明
<jats:title>Significance</jats:title> <jats:p>Traumatic brain injury (TBI) is a leading cause of long-term neurological disability and affects an ever-growing population. Currently, there are no effective treatments for patients suffering from chronic TBI-induced cognitive impairments. Here, we found that suppression of the integrated stress response (ISR) with a drug-like small-molecule inhibitor, ISRIB, rescued cognition in two TBI mouse models, even when administered weeks after injury. Consistent with the behavioral results, ISRIB restored long-term potentiation deficits observed in TBI mice. Our data suggest that targeting ISR activation could serve as a promising approach for the treatment of chronic cognitive dysfunction after TBI.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 114 (31), E6420-, 2017-07-10
Proceedings of the National Academy of Sciences