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The present review has shown the importance to María Ángel García Chaves
conduct continued basic molecular and preclinical studies.
Further along the road, clinical studies could show how an pharmacology. With personalised medicine looming in the
application could be made to diagnostics and future and the genetic and proteomic background of each
patient determining specific approaches, PKR could play
an extremely relevant clinical role.

Figure 7. Representative diagram of PKR activation and modulation: pathological consequences of an unbalanced PKR activity.

PKR is activated by a variety of cellular stresses including viral and bacterial infections, cytokines, and chemotherapeutic drugs. PKR
activation involves its autophosphorylation, which triggers the phosphorylation of translation initiation factor eIF2a and the activation of

the proinflammatory NF-kB transcription factor. Both effects contribute to induce apoptosis cell death or to induce cell proliferation

depending on the stimulus and unknown factors. In addition, PKR is involved in inflammasome activation and cytokines liberation as IL-
6, TNF a and HMGB among others. Moreover PKR is involved in various pathways that engage multiple genes, including MAPKs,

ATFs, STATs, and p53, among others. Diverse PKR modulators have been identified, highlighting the PKR activator PACT, the inhibitor

TRBP, and the microRNA mir886. An unbalanced effect induced by dysregulated PKR activity could contribute to neurodegeneration,

cancer and inflammatory diseases.

5. ACKNOWLEDGEMENTS 2. Garcia MA, Meurs EF, Esteba M. The dsRNA protein
kinase PKR: Virus and cell control.Biochimie 2006;
The author is thankful to members of the Drs Esteban 89:799-811.
and Marchal groups who worked on the PKR project for
their contribution. Special thanks to Dr Esteban for giving 3. Samuel CE. Antiviral actions of interferon. Interferon-
me the opportunity to work in the exciting world of PKR regulated cellular proteins and their surprisingly
kinase, and special thanks to Dr Marchal to facilitate my selective antiviral activities. Virology 1991;183(1):1-
leadership in this research. Garcia MA is funded by the 11.
Andalusian regional government and the Carlos III
Institute of Health. 4. Pestka S, Krause CD, Walter MR. Interferons,
interferon-like cytokines, and their receptors.
6. REFERENCES Immunol Rev 2004;202:8-32.

1. Garcia MA, Gil J, Ventoso I, et al. Impact of protein 5. Borden EC, Williams BR. Interferon-stimulated genes
kinase PKR in cell biology: from antiviral to and their protein products: what and how?. J
antiproliferative action. Microbiol Mol Biol Rev 2006; Interferon Cytokine Res 2011;31(1):1-4.

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160 @Real Academia Nacional de Farmacia. Spain