Prion protein induced signaling cascades in monocytes

Krebs, Bjarne; Dorner-Ciossek, Cornelia; Schmalzbauer, Rüdiger; Vassallo, Neville; Herms, Jochen; Kretzschmar, Hans A.

doi:10.1016/j.bbrc.2005.11.158

Cited by 43 publications

(53 citation statements)

References 72 publications

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“…This was interesting in view of reports that PrP C seems to be involved in the activation of p44/42 MAPK and Akt during macrophage phagocytosis. 26,27 Hence, modulation of macrophage p44/42 MAPK and Akt by PrP C might be of significance in colitis. The higher levels of pro-survival molecules such as phospho-Akt in the inflamed colons of Tga20 mice were consistent with previous observations of phosphatidylinositol 3-kinase pathway activity regulation by PrP C7,15 and could account, at least in part, for the milder colonic disease manifested by these PrP C overexpressing animals.…”

Section: Discussionmentioning

confidence: 99%

“…For example, it has been recently demonstrated that PrP C is involved in modulating T-cell activation and proliferation 18,25 and the phagocytic activity of macrophages. 26,27 Moreover, depletion of PrP C skews T cells toward the helper T cell type 1 (Th1) and type 17 (Th17) phenotypes. 18,19 This is of significance because these lineages produce a variety of proinflammatory cytokines that are up-regulated in the intestinal mucosa in individuals with inflammatory bowel disease.…”

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confidence: 99%

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Endogenous Prion Protein Attenuates Experimentally Induced Colitis

Martin

Keenan

Sharkey

et al. 2011

The American Journal of Pathology

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Although the cellular prion protein (PrP C ) is expressed in the enteric nervous system and lamina propria, its function(s) in the gut is unknown. Because PrP C may exert a cytoprotective effect in response to various physiologic stressors, we hypothesized that PrP C expression levels might modulate the severity of experimental colitis. We evaluated the course of dextran sodium sulfate (DSS)-induced colitis in hemizygous Tga20 transgenic mice (approximately sevenfold overexpression of PrP C ), Prnp ؊/؊ mice, and wild-type mice. On day 7, colon length, disease severity, and histologic activity indices were determined. Unlike DSS-treated wild-type and Prnp ؊/؊ animals, PrP C overexpressing mice were resistant to colitis induction, exhibited much milder histopathologic features, and did not exhibit weight loss or colonic shortening. In keeping with these results, pro-survival molecule expression and/or phosphorylation levels were elevated in DSStreated Tga20 mice, whereas pro-inflammatory cytokine production and pSTAT3 levels were reduced. In contrast, DSS-treated Prnp ؊/؊ mice exhibited increased BAD protein expression and a cytokine expression profile predicted to favor inflammation and differentiation. PrP C expression from both the endogenous Prnp locus or the Tga20 transgene was increased in the colons of DSStreated mice. Considered together, these findings demonstrate that PrP C has a previously unrecognized cytoprotective and/or anti-inflammatory function within the murine colon.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Endogenous Prion Protein Attenuates Experimentally Induced Colitis

Martin

Keenan

Sharkey

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

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“…Other in vivo and in vitro studies have shown a close relationship between PrP and both the development/differentiation of neurons and synaptic formation due to PrP-induced signal transduction in axonal/dendritic growth (Dürig et al, 2000;Burthem et al, 2001;Li et al, 2001). Moreover, PrP may also participate in the regulation, proliferation, and differentiation of neural progenitors, thereby playing a role in neurogenesis (Stahl et al, 1987;Prusiner, 1991;Krebs et al, 2006). In this study, the levels of PrP mRNA in the CSF differed significantly between the healthy individuals and the PD patients.…”

Section: Discussionmentioning

confidence: 53%

Expression of prion protein in the cerebrospinal fluid of patients with Parkinson’s disease complicated with rapid eye movement sleep behavior disorder

Zhang

Shang

et al. 2017

Genet. Mol. Res.

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ABSTRACT. Parkinson's disease (PD) is one of the most common neurodegenerative diseases and mainly manifests with decreasing numbers of dopaminergic neurons. Rapid eye movement (REM) sleep behavior disorder (RBD) has an incidence of 15-47% in all PD patients. Prion proteins (PrPs), which are expressed in both neurons and glial cells of the brain, are believed to be correlated with abnormal neurological functions, although their role in PD-related sleeping disorders remains unclear. We therefore investigated the expressional profiles of PrP in PD patients with RBD. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein levels of PrP, respectively, in the cerebrospinal fluid (CSF) of PD patients with RBD, PD patients without sleeping disorder, and healthy people (N = 23 each). We investigated the correlation between the CSF PrP level and sleeping behavior in PD patients. Patients with PD complicated with RBD had significantly elevated CSF PrP expression levels (both mRNA and protein) compared with either PD patients without sleeping disorder or healthy individuals (P < 0.05 in both cases). There is elevated expression of PrP in the CSF of PD patients with RBD. This may benefit the diagnosis of PD-related RBD.

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“…41 In addition, Almeida et al 42 report that macrophages from mice with depletion of the Prnp gene show higher rates of phagocytosis than wild-type macrophages in in vitro and in vivo assays, and that the activation of ERK-1/2 and Akt kinase induce various biological responses of macrophages in PrP-knockout mouse. 43 Dendritic cells and macrophages in SED would immediately degrade incorporated PrP c . 44,45 These results indicate that the undigested PrP Sc may induce the accumulation of PrP-positive cells in the subfollicle region of Peyer's patches and their spread to the MLN and the spleen.…”

Section: Discussionmentioning

confidence: 99%