The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Pharmacological brake-release of mRNA translation enhances cognitive memory
Open accessAbstract
Phosphorylation of the α-subunit of initiation factor 2 (eIF2) controls protein synthesis by a conserved mechanism. In metazoa, distinct stress conditions activate different eIF2α kinases (PERK, PKR, GCN2, and HRI) that converge on phosphorylating a unique serine in eIF2α. This collection of signaling pathways is termed the ‘integrated stress response’ (ISR). eIF2α phosphorylation diminishes protein synthesis, while allowing preferential translation of some mRNAs. Starting with a cell-based screen for inhibitors of PERK signaling, we identified a small molecule, named ISRIB, that potently (IC50 = 5 nM) reverses the effects of eIF2α phosphorylation. ISRIB reduces the viability of cells subjected to PERK-activation by chronic endoplasmic reticulum stress. eIF2α phosphorylation is implicated in memory consolidation. Remarkably, ISRIB-treated mice display significant enhancement in spatial and fear-associated learning. Thus, memory consolidation is inherently limited by the ISR, and ISRIB releases this brake. As such, ISRIB promises to contribute to our understanding and treatment of cognitive disorders.
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Harding, H. P., Zhang, Y., Bertolotti, A., Zeng, H., & Ron, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80330-5 · Cited by 2,021
A unifying model for mTORC1-mediated regulation of mRNA translation
Thoreen, C. C., Chantranupong, L., Keys, H. R., Wang, T., Gray, N. S., & Sabatini, D. M. (2012) · Nature · doi:10.1038/nature11083 · Cited by 1,477
PKMζ maintains memories by regulating GluR2-dependent AMPA receptor trafficking
Migues, P. V., Hardt, O., Wu, D. C., Gamache, K., Sacktor, T. C., Wang, Y. T., & Nader, K. (2010) · Nature Neuroscience · doi:10.1038/nn.2531 · Cited by 283
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Cited by
The integrated stress response
Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659
Mechanisms, regulation and functions of the unfolded protein response
Hetz, C., Zhang, K., & Kaufman, R. J. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0250-z · Cited by 2,666
Protein misfolding in the endoplasmic reticulum as a conduit to human disease
Wang, M., & Kaufman, R. J. (2016) · Nature · doi:10.1038/nature17041 · Cited by 1,630
The integrated stress response: From mechanism to disease
Costa-Mattioli, M., & Walter, P. (2020) · Science · doi:10.1126/science.aat5314 · Cited by 1,617
Self-citationDisturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Hetz, C., & Mollereau, B. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3689 · Cited by 684
Metadata
- Authors
- Sidrauski, C., Acosta-Alvear, D., Khoutorsky, A., Vedantham, P., Hearn, B. R., Li, H., Gamache, K., Gallagher, C. M., Ang, K. K.-H., Wilson, C., Okreglak, V., Ashkenazi, A., Hann, B., Nader, K., Arkin, M. R., Renslo, A. R., Sonenberg, N., & Walter, P.
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2013-05-28
- Volume
- 2
- Pages
- e00498-e00498
- ISSN
- 2050-084X (ISSN-L)
- OpenAlex
- W2067040999
- Cited by
- 725
- References
- 3
- FWCI
- 19.23
- Type
- journal article
- Language
- en
- Open access
- gold
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- Sidrauski, C., Acosta-Alvear, D., Khoutorsky, A., Vedantham, P., Hearn, B. R., Li, H., Gamache, K., Gallagher, C. M., Ang, K. K.-H., Wilson, C., Okreglak, V., Ashkenazi, A., Hann, B., Nader, K., Arkin, M. R., Renslo, A. R., Sonenberg, N., & Walter, P. (2013). Pharmacological brake-release of mRNA translation enhances cognitive memory. eLife. https://doi.org/10.7554/elife.00498
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