The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration.
| Autor: | Martinez NW; Fundación Ciencia & Vida, Santiago, Chile.; Departamento de Ciencias Básicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile., Gómez FE; Fundación Ciencia & Vida, Santiago, Chile., Matus S; Fundación Ciencia & Vida, Santiago, Chile.; Departamento de Ciencias Básicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile.; Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile.; Center for Geroscience, Brain Health and Metabolism, Santiago, Chile. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in aging neuroscience [Front Aging Neurosci] 2021 Apr 28; Vol. 13, pp. 638208. Date of Electronic Publication: 2021 Apr 28 (Print Publication: 2021). |
| DOI: | 10.3389/fnagi.2021.638208 |
| Abstrakt: | There is a growing evidence describing a decline in adaptive homeostasis in aging-related diseases affecting the central nervous system (CNS), many of which are characterized by the appearance of non-native protein aggregates. One signaling pathway that allows cell adaptation is the integrated stress response (ISR), which senses stress stimuli through four kinases. ISR activation promotes translational arrest through the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) and the induction of a gene expression program to restore cellular homeostasis. However, depending on the stimulus, ISR can also induce cell death. One of the ISR sensors is the double-stranded RNA-dependent protein kinase [protein kinase R (PKR)], initially described as a viral infection sensor, and now a growing evidence supports a role for PKR on CNS physiology. PKR has been largely involved in the Alzheimer's disease (AD) pathological process. Here, we reviewed the antecedents supporting the role of PKR on the efficiency of synaptic transmission and cognition. Then, we review PKR's contribution to AD and discuss the possible participation of PKR as a player in the neurodegenerative process involved in aging-related pathologies affecting the CNS. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Martinez, Gómez and Matus.) |
| Databáze: | MEDLINE |
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