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

Hdl Handle:
http://hdl.handle.net/10147/201228
Title:
Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.
Authors:
Paquet, Claire; Bose, Anindita; Polivka, Marc; Peoc'h, Katell; Brouland, Jean Philippe; Keohane, Catherine; Hugon, Jacques; Gray, Françoise
Affiliation:
Service Central d'Anatomie et de Cytologie Pathologiques, APHP, Hôpital Lariboisière-Université Paris VII, France.
Citation:
Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease. 2009, 68 (2):190-8 J. Neuropathol. Exp. Neurol.
Journal:
Journal of neuropathology and experimental neurology
Issue Date:
Feb-2009
URI:
http://hdl.handle.net/10147/201228
DOI:
10.1097/NEN.0b013e318196cd7c
PubMed ID:
19151623
Abstract:
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.
Item Type:
Article
Language:
en
Description:
A comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height, maxillary base and ascending ramus were found to be significantly decreased in men with Klinefelter syndrome when compared to the male control group. Significant differences in the lengths of mandibular base and posterior cranial base were not found. When compared to the female control, all structures examined were significantly increased, except for the maxillary base.
MeSH:
Aged; Aged, 80 and over; Apoptosis; Brain; Caspase 3; Cell Nucleus; Creutzfeldt-Jakob Syndrome; Female; Glial Fibrillary Acidic Protein; Gliosis; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Male; Middle Aged; Nerve Degeneration; Neurons; Phosphorylation; Prions; Stress, Physiological; eIF-2 Kinase
ISSN:
0022-3069

Full metadata record

DC FieldValue Language
dc.contributor.authorPaquet, Claireen
dc.contributor.authorBose, Aninditaen
dc.contributor.authorPolivka, Marcen
dc.contributor.authorPeoc'h, Katellen
dc.contributor.authorBrouland, Jean Philippeen
dc.contributor.authorKeohane, Catherineen
dc.contributor.authorHugon, Jacquesen
dc.contributor.authorGray, Françoiseen
dc.date.accessioned2012-01-10T12:50:05Z-
dc.date.available2012-01-10T12:50:05Z-
dc.date.issued2009-02-
dc.identifier.citationNeuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease. 2009, 68 (2):190-8 J. Neuropathol. Exp. Neurol.en
dc.identifier.issn0022-3069-
dc.identifier.pmid19151623-
dc.identifier.doi10.1097/NEN.0b013e318196cd7c-
dc.identifier.urihttp://hdl.handle.net/10147/201228-
dc.descriptionA comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height, maxillary base and ascending ramus were found to be significantly decreased in men with Klinefelter syndrome when compared to the male control group. Significant differences in the lengths of mandibular base and posterior cranial base were not found. When compared to the female control, all structures examined were significantly increased, except for the maxillary base.en
dc.description.abstractThe 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.-
dc.language.isoenen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshApoptosis-
dc.subject.meshBrain-
dc.subject.meshCaspase 3-
dc.subject.meshCell Nucleus-
dc.subject.meshCreutzfeldt-Jakob Syndrome-
dc.subject.meshFemale-
dc.subject.meshGlial Fibrillary Acidic Protein-
dc.subject.meshGliosis-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshIn Situ Nick-End Labeling-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNerve Degeneration-
dc.subject.meshNeurons-
dc.subject.meshPhosphorylation-
dc.subject.meshPrions-
dc.subject.meshStress, Physiological-
dc.subject.mesheIF-2 Kinase-
dc.titleNeuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.en
dc.typeArticleen
dc.contributor.departmentService Central d'Anatomie et de Cytologie Pathologiques, APHP, Hôpital Lariboisière-Université Paris VII, France.en
dc.identifier.journalJournal of neuropathology and experimental neurologyen
dc.description.provinceMunster-

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