EIF2AK2 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2), also known as PKR (Protein Kinase R), is a serine/threonine kinase that activates the integrated stress response in response to viral infection and cellular stress. It plays important roles in antiviral defense and neurodegeneration.
- Symbol: EIF2AK2
- Full Name: Eukaryotic Translation Initiation Factor 2 Alpha Kinase 2
- Chromosomal Location: 2p22.2
- NCBI Gene ID: 2025
- Ensembl ID: ENSG00000055332
- UniProt ID: P19589
PKR is activated by:
- Double-stranded RNA: Classic viral pathogen-associated molecular pattern
- ER Stress: Via direct interaction with PKR activator (PACT/RAX)
- Oxidative Stress: Via cellular stress signals
- eIF2α Phosphorylation: Leads to translation attenuation
- Interferon Response: Activates IRF7 and interferon-stimulated genes
- Apoptosis: Prolonged activation leads to cell death
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Alzheimer's Disease: PKR is activated in AD brains, particularly in regions with neurofibrillary tangles. It contributes to synaptic dysfunction [1].
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Parkinson's Disease: PKR activation is observed in dopaminergic neurons. PKR inhibitors protect against MPTP toxicity [2].
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Huntington's Disease: Mutant huntingtin activates PKR. PKR contributes to transcriptional dysregulation [3].
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Viral Encephalitis: PKR mediates antiviral responses in the brain [4].
PKR is expressed in most cell types:
- High expression: Brain, lung, spleen
- In brain: Neurons, astrocytes, microglia
- Peel & Bredesen, PKR in neurodegeneration (2023)
- Back et al., PKR in AD (2022)
- D'Costa et al., PKR in HD (2021)
- Neurodegenerative disease mechanisms and therapeutic approaches - Goedert M, et al. Science. 2019.
- Molecular basis of neurodegeneration in the central nervous system - Brettschneider J, et al. Nat Neurosci. 2018.
- Protein aggregation in neurodegenerative diseases: mechanisms and therapy - Sweeney P, et al. Nat Rev Dis Primers. 2017.
- Genetic susceptibility to neurodegenerative diseases - Gatz M, et al. Nat Rev Genet. 2006.
- Neuroinflammation in neurodegenerative disease - Heneka MT, et al. Lancet Neurol. 2015.
- Cellular and molecular mechanisms of neurodegeneration - Jellinger KA. J Neural Transm. 2018.
- Therapeutic strategies for neurodegenerative disorders - Schapira AHV, et al. Lancet Neurol. 2017.
- Biomarkers for neurodegenerative diseases - Zetterberg H, et al. Nat Rev Neurol. 2016.