RGD Reference Report - Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease. - Rat Genome Database

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Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.

Authors: Paquet, C  Bose, A  Polivka, M  Peoc'h, K  Brouland, JP  Keohane, C  Hugon, J  Gray, F 
Citation: Paquet C, etal., J Neuropathol Exp Neurol. 2009 Feb;68(2):190-8. doi: 10.1097/NEN.0b013e318196cd7c.
RGD ID: 10395347
Pubmed: PMID:19151623   (View Abstract at PubMed)
DOI: DOI:10.1097/NEN.0b013e318196cd7c   (Journal Full-text)

The mechanisms of neuronal apoptosis in Creutzfeldt-Jakob disease (CJD) and their relationship to accumulated prion protein (PrP) are unclear. A recent cell culture study showed that intracytoplasmic PrP may induce phosphorylated RNA-dependent protein kinase (PKR(p))-mediated cell stress. The double-stranded RNA protein kinase PKR is a proapoptotic and stress kinase that accumulates in degenerating neurons in Alzheimer disease. To determine whether neuronal apoptosis in human CJD is associated with activation of the PKR(p) signaling pathway, we assessed in situ end labeling and immunocytochemistry for PrP, glial fibrillary acidic protein, CD68, activated caspase 3, and phosphorylated PKR (Thr451) in samples of frontal, occipital, and temporal cortex, striatum, and cerebellum from 6 patients with sporadic CJD and 5 controls. Neuronal immunostaining for activated PKR was found in all CJD cases. The most staining was in nuclei and, in contrast to findings in Alzheimer disease, cytoplasmic labeling was not detected. Both the number and distribution of PKR(p)-positive neurons correlated closely with the extent of neuronal apoptosis, spongiosis, astrocytosis, and microglial activation and with the phenotype and disease severity. There was no correlation with the type, topography, or amount of extracellular PrP deposits. These findings suggest that neuronal apoptosis in human CJD may result from PKR(p)-mediated cell stress and are consistent with recent studies supporting a pathogenic role for intracellular or transmembrane PrP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Sporadic Creutzfeldt-Jakob Disease  IDA 10395347 RGD 
Sporadic Creutzfeldt-Jakob Disease  ISOEIF2AK2 (Homo sapiens)10395347; 10395347 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eif2ak2  (eukaryotic translation initiation factor 2-alpha kinase 2)

Genes (Mus musculus)
Eif2ak2  (eukaryotic translation initiation factor 2-alpha kinase 2)

Genes (Homo sapiens)
EIF2AK2  (eukaryotic translation initiation factor 2 alpha kinase 2)


Additional Information