• Stefania Beretta, Laura Gritti, Chiara Verpelli, and Carlo Sala.
• CNR Neuroscience Institute, Milano, Italy.
• Neuroscience. 2020 Oct 1; 445: 42-49.

AbstractTwo major processes tightly regulate protein synthesis, the initiation of mRNA translation and elongation phase that mediates the movement of ribosomes along the mRNA. The elongation phase is a high energy-consuming process, and is mainly regulated by the eukaryotic elongation factor 2 kinase (eEF2K) activity that phosphorylates and inhibits eEF2, the only known substrate of the kinase. eEF2K activity is closely regulated by several signaling pathways because the translation elongation phase strongly influences the cellular energy demand and can change the expression of specific proteins in different tissues. An increasing number of recent findings link eEF2k over activation to an array of human diseases, such as atherosclerosis, pulmonary arterial hypertension, progression of solid tumors, and some major neurological disorders. Several neurological studies suggest that eEF2K is a valuable target in treating epilepsy, depression and major neurodegenerative diseases. Despite eEF2k is an ubiquitous and conserved protein, it has been proved that its deletion does not affect development in animal models and in general cell viability. Therefore, it is possible to postulate that inhibiting its function may not cause serious side effects. In addition, eEF2K is a peculiar kinase molecularly different from most of other mammalian kinases and new compounds that inhibit eEF2K should not necessarily interfere with other important protein kinases. In this review we will critically summarize the evidence supporting the role of the altered eEF2K/eEF2 pathway in defined neurological diseases and its implications in curing these diseases in animal models, and possibly in humans, by targeting eEF2K activity.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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