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Functional characterisation of the eIF2alpha, GCN2 and PERK kinases in the molecular memory mechanisms

14th national competition for scientific and technical research

Molecular memory mechanisms

Senior Researcher : César de Haro Castella

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Research Centre or Institution : Centro de Biología Molecular "Severo Ochoa". CSIC-Universidad Autónoma de Madrid


It is known that factor 2 alpha subunit (eIF2-alpha) phosphorylation by specific kinase proteins (GCN2, PERK, HRI and PKR) is directly involved in controlling translation in eukaryotic cells. These eIF2-alpha kinases act in response to different cellular stress situations. Our research group identified, cloned and characterised mammalian GCN2 and has recently proven its role in the central nervous system's anti-viral response to RNA virus tropism. A paper published in the prestigious magazine Nature shows how GCN2 is involved in the regulation of synaptic plasticity, learning and memory. Other results indicate that eIF2-alpha phosphorylation is associated to neuronal degeneration in Alzheimer's Disease and is involved in the pathophysiology of Parkinson's Disease. However, the effect of GCN2, and possibly that of PERK, on learning and memory at the molecular level remains unknown. Our objective is to study the molecular activation mechanisms of these eIF2-alpha kinases (GCN2, PERK), through the identification of proteins that interact with them, thereby modulating their activity. Some of the new proteins identified could serve as a therapeutic target for some of these neurodegenerative diseases. In any case, achievement of the objectives established for this project will help improve our understanding of these processes.

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