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

Détails

ID Serval
serval:BIB_907F98576225
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.
Périodique
Journal of Neuropathology and Experimental Neurology
Auteur⸱e⸱s
Paquet C., Bose A., Polivka M., Peoc'h K., Brouland J.P., Keohane C., Hugon J., Gray F.
ISSN
0022-3069 (Print)
ISSN-L
0022-3069
Statut éditorial
Publié
Date de publication
2009
Peer-reviewed
Oui
Volume
68
Numéro
2
Pages
190-198
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
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.
Mots-clé
Aged, Aged, 80 and over, Apoptosis/physiology, Brain/enzymology, Brain/pathology, Caspase 3/analysis, Caspase 3/metabolism, Cell Nucleus/enzymology, Cell Nucleus/pathology, Creutzfeldt-Jakob Syndrome/enzymology, Creutzfeldt-Jakob Syndrome/genetics, Female, Glial Fibrillary Acidic Protein/analysis, Glial Fibrillary Acidic Protein/metabolism, Gliosis/enzymology, Gliosis/etiology, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Male, Middle Aged, Nerve Degeneration/enzymology, Nerve Degeneration/etiology, Neurons/enzymology, Neurons/pathology, Phosphorylation, Prions/analysis, Prions/metabolism, Stress, Physiological/physiology, eIF-2 Kinase/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/10/2015 9:56
Dernière modification de la notice
20/08/2019 14:53
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