Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity

Weise, Jens; Crome, Olaf; Sandau, Raoul; Schulz‐Schaeffer, Walter; Bähr, Mathias; Zerr, Inga

doi:10.1016/j.neulet.2004.09.030

Cited by 128 publications

(112 citation statements)

References 28 publications

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“…These observations indicate that AQP4 is helpful in combating vasogenic cerebral edema, but detrimental in cases of cytotoxic edema. PrP C expression is upregulated following focal cerebral ischemia [47], a model of cytotoxic edema, and PrP C deletion leads to worsened outcome following ischemic brain injury [48,49]. This supports the theory that loss of PrP C function late in prion disease pathogenesis results in increased AQP4 expression, since increased AQP4 expression would be detrimental following ischemic brain injury.…”

Section: The Appearance Of Spongiform Change Prpsupporting

confidence: 64%

Pre-Clinical Changes Observed by Magnetic Resonance Imaging in a Hamster Model of Transmissible Spongiform Encephalopathy: a Potential Biomarker of Prion Infection

Baydack¹,

McKenzie²,

Robertson³

2011

J Mol Biomark Diagn

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The objective of the study was to develop a model for the diagnosis of prion diseases in live animals, using magnetic resonance imaging (MRI). Hamsters experimentally infected with the 263K strain of scrapie were imaged periodically during the course of prion infection. Changes in the brain, particularly the hippocampus, were observed during the first quarter of the incubation period. These changes included an increase in T 2 relaxation time and apparent diffusion coefficient (ADC), indicative of an increase in the water content of tissues. These changes were apparent well before the appearance of clinical symptoms, and did not correlate with the typical histological changes characteristic of prion disease, (vacuolation, accumulation of PrP protein, gliosis) suggesting that the changes are caused by a progressive accumulation of fluid. This oedema may be a novel early marker of prion disease, and could play a role in pathogenesis.

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Section: The Appearance Of Spongiform Change Prpsupporting

confidence: 64%

Pre-Clinical Changes Observed by Magnetic Resonance Imaging in a Hamster Model of Transmissible Spongiform Encephalopathy: a Potential Biomarker of Prion Infection

Baydack¹,

McKenzie²,

Robertson³

2011

J Mol Biomark Diagn

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“…Some investigators found that, under ischemic conditions, PrP C expression is upregulated (McLennan et al, 2004;Weise et al, 2004). These previous in vivo results, in either the human or rodent brain, indicate that PrP C has a protective role against neurotoxicity.…”

Section: Discussionmentioning

confidence: 90%

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Shyu¹,

Lin²,

Chiang³

et al. 2005

J. Neurosci.

116

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Prion diseases are induced by pathologically misfolded prion protein (PrPSc ), which recruit normal sialoglycoprotein PrP C by a templatedirected process. In this study, we investigated the expression of PrP C in a rat model of cerebral ischemia to more fully understand its physiological role. Immunohistochemical analysis demonstrated that PrP C -immunoreactive cells increased significantly in the penumbra of ischemic rat brain compared with the untreated brain. Western blot analysis showed that PrP C protein expression increased in ischemic brain tissue in a time-dependent manner. In addition, PrP C protein expression was seen to colocalize with neuron, glial, and vascular endothelial cells in the penumbric region of the ischemic brain. Overexpression of PrP C by injection of rAd (replication-defective recombinant adenoviral)-PGK (phosphoglycerate kinase)-PrP C -Flag into ischemic rat brain improved neurological behavior and reduced the volume of cerebral infarction, which is supportive of a role for PrP C in the neuroprotective adaptive cellular response to ischemic lesions. Concomitant upregulation of PrP C and activated extracellular signal-regulated kinase (ERK1/2) under hypoxia-reoxygenation in primary cortical cultures was shown to be dependent on ERK1/2 phosphorylation. During hypoxia-reoxygenation, mouse neuroblastoma cell line N18 cells transfected with luciferase rat PrP C promoter reporter constructs, containing the heat shock element (HSE), expressed higher luciferase activities (3-to 10-fold) than those cells transfected with constructs not containing HSE. We propose that HSTF-1 (hypoxia-activated transcription factor), phosphorylated by ERK1/2, may in turn interact with HSE in the promoter of PrP C resulting in gene expression of the prion gene. In summary, we conclude that upregulation of PrP C expression after cerebral ischemia and hypoxia exerts a neuroprotective effect on injured neural tissue. This study suggests that PrP C has physiological relevance to cerebral ischemic injury and could be useful as a therapeutic target for the treatment of cerebral ischemia.

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“…In the last decade a diverse range of functions has been attributed to the native PrP C protein, such as neuroprotection against cellular and systemic insults, neuritogenesis, neuronal plasticity and excitability, and memory formation and consolidation (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Noteworthy, PrP C mutations associated to CJD, fatal familial insomnia, and Gerstmann-Straussler-Scheinker disease decrease or abolish the anti-bax function in primary human neurons and breast cancer cell lines promoting programmed cell death (34).…”

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confidence: 99%

Disease-associated Mutations in the Prion Protein Impair Laminin-induced Process Outgrowth and Survival

Machado

Beraldo

Santos

et al. 2012

Journal of Biological Chemistry

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Background: In addition to the toxicity mediated by prion protein misfolding, mechanisms associated with its loss-offunction in genetic prion diseases are unknown. Results: Neural cells expressing PrP C mutants associated with prion diseases present impaired laminin-mediated process outgrowth and survival. Conclusion: PrP C mutants show loss-of-function in neural cells. Significance: The impairment of prion protein functions may contribute to the etiology of prion diseases.

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Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity

Cited by 128 publications

References 28 publications

Pre-Clinical Changes Observed by Magnetic Resonance Imaging in a Hamster Model of Transmissible Spongiform Encephalopathy: a Potential Biomarker of Prion Infection

Pre-Clinical Changes Observed by Magnetic Resonance Imaging in a Hamster Model of Transmissible Spongiform Encephalopathy: a Potential Biomarker of Prion Infection

Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Disease-associated Mutations in the Prion Protein Impair Laminin-induced Process Outgrowth and Survival

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Upregulation of cellular prion protein (PrPc) after focal cerebral ischemia and influence of lesion severity

Cited by 128 publications

References 28 publications

Pre-Clinical Changes Observed by Magnetic Resonance Imaging in a Hamster Model of Transmissible Spongiform Encephalopathy: a Potential Biomarker of Prion Infection

Pre-Clinical Changes Observed by Magnetic Resonance Imaging in a Hamster Model of Transmissible Spongiform Encephalopathy: a Potential Biomarker of Prion Infection

Overexpression of PrPCby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model

Disease-associated Mutations in the Prion Protein Impair Laminin-induced Process Outgrowth and Survival

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Overexpression of PrP^Cby Adenovirus-Mediated Gene Targeting Reduces Ischemic Injury in a Stroke Rat Model