The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration
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 stres...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Aging Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.638208/full |
| _version_ | 1819077259974148096 |
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| author | Nicolás W. Martinez Nicolás W. Martinez Nicolás W. Martinez Nicolás W. Martinez Felipe E. Gómez Soledad Matus Soledad Matus Soledad Matus Soledad Matus |
| author_facet | Nicolás W. Martinez Nicolás W. Martinez Nicolás W. Martinez Nicolás W. Martinez Felipe E. Gómez Soledad Matus Soledad Matus Soledad Matus Soledad Matus |
| author_sort | Nicolás W. Martinez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T18:54:22Z |
| format | Article |
| id | doaj.art-d7bc06f3cade47ff88c720f8e282f888 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-21T18:54:22Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-d7bc06f3cade47ff88c720f8e282f8882022-12-21T18:53:39ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-04-011310.3389/fnagi.2021.638208638208The Potential Role of Protein Kinase R as a Regulator of Age-Related NeurodegenerationNicolás W. Martinez0Nicolás W. Martinez1Nicolás W. Martinez2Nicolás W. Martinez3Felipe E. Gómez4Soledad Matus5Soledad Matus6Soledad Matus7Soledad Matus8Fundación Ciencia & Vida, Santiago, ChileDepartamento de Ciencias Básicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, ChileCenter for Geroscience, Brain Health and Metabolism, Santiago, ChileFundación Ciencia & Vida, Santiago, ChileFundación Ciencia & Vida, Santiago, ChileDepartamento de Ciencias Básicas, Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, ChileBiomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, ChileCenter for Geroscience, Brain Health and Metabolism, Santiago, ChileThere 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.https://www.frontiersin.org/articles/10.3389/fnagi.2021.638208/fulldouble-stranded RNA-dependent protein kinaseintegrated stress responseneurocognitive functionsAlzheimer’s diseaseParkinson’s diseaseHuntington’s disease |
| spellingShingle | Nicolás W. Martinez Nicolás W. Martinez Nicolás W. Martinez Nicolás W. Martinez Felipe E. Gómez Soledad Matus Soledad Matus Soledad Matus Soledad Matus The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration Frontiers in Aging Neuroscience double-stranded RNA-dependent protein kinase integrated stress response neurocognitive functions Alzheimer’s disease Parkinson’s disease Huntington’s disease |
| title | The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration |
| title_full | The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration |
| title_fullStr | The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration |
| title_full_unstemmed | The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration |
| title_short | The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration |
| title_sort | potential role of protein kinase r as a regulator of age related neurodegeneration |
| topic | double-stranded RNA-dependent protein kinase integrated stress response neurocognitive functions Alzheimer’s disease Parkinson’s disease Huntington’s disease |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.638208/full |
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