In:
eLife, eLife Sciences Publications, Ltd, Vol. 2 ( 2013-05-28)
Abstract:
The synthesis of proteins is an essential step in many biological processes, including memory, and drugs that inhibit protein synthesis are known to impair memory in rodents. It is thought that the brain needs these proteins to convert short-term memories into long-term memories through a process known as consolidation. A protein called EIF2α has a key role in the regulation of protein synthesis, and has also been implicated in memory. EIF2α can be activated as a result of being phosphorylated by any of four protein kinases: these are in turn activated by processes that subject cells to stress, such as viral infection, UV light or—in the case of a kinase known as PERK—the accumulation of unfolded proteins in a cellular organelle called the endoplasmic reticulum. Activation of EIF2α downregulates most protein synthesis inside the cell, but upregulates the production of a small number of key regulatory molecules: these changes help cells to cope with whatever stressful event they have just experienced. To obtain further insight into the cellular stress response, Sidrauski et al. screened a large library of compounds in search of one that inhibits PERK. They identified a molecule—known as ISRIB—which acts downstream of all four protein kinases by reversing the effects of EIF2α phosphorylation. ISRIB is the first molecule shown to have this effect, and thus represents an important tool for investigating the stress response inside cells. When Sidrauski et al. injected ISRIB into mice, the animals showed improved memory: for example, they learnt to locate a hidden platform in a water maze more rapidly than controls. This suggests that ISRIB could be used to explore the mechanisms that underlie memory consolidation, and possibly even as a memory enhancer. Moreover, given that many tumor cells exploit the cellular stress response to aid their own growth, ISRIB may have potential as a novel chemotherapeutic agent.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.00498.001
DOI:
10.7554/eLife.00498.002
DOI:
10.7554/eLife.00498.003
DOI:
10.7554/eLife.00498.004
DOI:
10.7554/eLife.00498.005
DOI:
10.7554/eLife.00498.006
DOI:
10.7554/eLife.00498.007
DOI:
10.7554/eLife.00498.008
DOI:
10.7554/eLife.00498.009
DOI:
10.7554/eLife.00498.010
DOI:
10.7554/eLife.00498.011
DOI:
10.7554/eLife.00498.012
DOI:
10.7554/eLife.00498.013
DOI:
10.7554/eLife.00498.014
DOI:
10.7554/eLife.00498.015
DOI:
10.7554/eLife.00498.016
DOI:
10.7554/eLife.00498.017
DOI:
10.7554/eLife.00498.018
DOI:
10.7554/eLife.00498.019
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2013
detail.hit.zdb_id:
2687154-3