PKR Activation in Neurodegenerative Disease
Abstract
Interferon-inducible, double-stranded RNA-dependent protein kinase PKR is well known as an early cellular responder to viral infection. Activation of PKR has been associated with a number of downstream cell stress and cell death events, including a generalized shutdown of protein translation, activation of caspase-8, participation in JNK and p38 MAPK pathways, activation of NF-kappaB, etc. Recently, the activation of PKR has also been described in several neurodegenerative diseases, including Huntington disease, Alzheimer disease, and amyotrophic lateral sclerosis. Although the relationship between PKR and these diseases is still unclear, the overlap between known functions of PKR and biochemical events that occur in these neuropathologies are discussed here.
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Phosphorylation of PKR and eIF2α is associated with degenerating neurons in AD brains.
“previous reports revealed that phosphorylation of PKR and eIF2α was associated with degenerating neurons in AD brains [50, 95, 96].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [96]
PKR is active in other neurodegenerative diseases, including Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis.
“PKR is not specific to AD because it is also known to be active in other neurodegenerative diseases like Parkinson's disease [49, 170], Huntington's disease [48] and amyotrophic lateral sclerosis [96].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [96]
Cites
Chang, R. C. C., Wong, A. K. Y., Ng, H.-K., & Hugon, J. (2002) · NeuroReport · doi:10.1097/00001756-200212200-00011 · Cited by 289 · see citing works
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The integrated stress response: From mechanism to disease
Costa-Mattioli, M., & Walter, P. (2020) · Science · doi:10.1126/science.aat5314 · Cited by 1,617 · see citing works
PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease
Morel, M., Couturier, J., Lafay‐Chebassier, C., Paccalin, M., & Page, G. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00849.x · Cited by 47 · see citing works
Damjanac, M., Page, G., Ragot, S., Laborie, G., Gil, R., Hugon, J., & Paccalin, M. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00688.x · Cited by 31 · see citing works
- Authors
- Peel, A. L.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Peel, Alyson L.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-02
- Volume
- 63
- Issue
- 2
- Pages
- 97-105
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- OpenAlex
- W50777772
- Cited by
- 67
- References
- 1
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 4 · 2018: 1 · 2017: 4 · 2016: 3 · 2014: 2 · 2013: 2 · 2012: 1
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- PKR, neurodegenerative diseases, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis, double-stranded RNA, caspase-8, MAPK signaling, NF-κB, cell death
- MeSH terms
- Aging, Animals, Humans, RNA, Double-Stranded, Stress, Physiological, Protein Biosynthesis, NF-kappa B, Apoptosis, Neurodegenerative Diseases, eIF-2 Kinase
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