INT204737

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Context Info
Confidence 0.59
First Reported 2007
Last Reported 2010
Negated 2
Speculated 0
Reported most in Body
Documents 32
Total Number 50
Disease Relevance 18.96
Pain Relevance 1.03

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Golgi apparatus (Prnp) endoplasmic reticulum (Prnp) nucleolus (Prnp)
plasma membrane (Prnp) nucleus (Prnp) cytoplasm (Prnp)
Anatomy Link Frequency
neurons 8
spleen 4
hippocampus 3
neuronal 2
brain 2
Prnp (Mus musculus)
Pain Link Frequency Relevance Heat
Thalamus 76 99.00 Very High Very High Very High
Lasting pain 19 98.28 Very High Very High Very High
Spinal cord 18 98.08 Very High Very High Very High
Hippocampus 50 96.76 Very High Very High Very High
ischemia 22 96.20 Very High Very High Very High
agonist 36 83.52 Quite High
Central nervous system 41 79.24 Quite High
Eae 3 72.16 Quite High
Glutamate 18 66.72 Quite High
Inflammation 25 57.28 Quite High
Disease Link Frequency Relevance Heat
Targeted Disruption 193 100.00 Very High Very High Very High
Creutzfeldt Jakob Disease 445 99.98 Very High Very High Very High
Stress Incontinence 70 99.88 Very High Very High Very High
Scrapie 412 99.84 Very High Very High Very High
Neuroblastoma 26 99.84 Very High Very High Very High
Prion Diseases 375 99.74 Very High Very High Very High
Infection 363 99.72 Very High Very High Very High
Disease Progression 82 99.32 Very High Very High Very High
Pain 20 98.28 Very High Very High Very High
Amyloid Plaque 20 97.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We found a decrease in Prnp expression in the lesion area while the infarct-free region around the lesion of the ipsilateral hemisphere showed a significant increase.
Negative_regulation (decrease) of Gene_expression (expression) of Prnp
1) Confidence 0.59 Published 2007 Journal Brain Pathology (Zurich, Switzerland) Section Body Doc Link PMC1859984 Disease Relevance 0.23 Pain Relevance 0.09
Another group created transgenic mice stably expressing PrP shRNA that reduced PrPC expression five-fold, although they did not assess prion disease in these animals [25].
Negative_regulation (reduced) of Gene_expression (expression) of PrPC associated with targeted disruption and prion diseases
2) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.67 Pain Relevance 0
Importantly, though, RNAi treatment in all of these model systems dramatically impeded PrPRES replication by reducing PrPC expression by more than 50%, an expression threshold shown to dramatically delay disease onset [11], [12], [13], [14].
Negative_regulation (reducing) of Gene_expression (expression) of PrPC associated with disease
3) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.82 Pain Relevance 0
In this study, we have begun to explore the possibility of using LSPCs injected iv to deliver PrPC siRNA across the BBB to all areas of the brain to suppress PrPC expression on neurons to protect them from prion diseases.
Negative_regulation (suppress) of Gene_expression (expression) of PrPC in neurons associated with prion diseases
4) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.59 Pain Relevance 0
This method also lacks desired temporal control of PrPC expression, since once brain cells are infected with lentivirus, it will likely irreversibly suppress PrPC expression in these cells.
Negative_regulation (suppress) of Gene_expression (expression) of PrPC in brain
5) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.57 Pain Relevance 0
Briefly, we enriched for N2a cells lacking endogenous PrPC expression (N?
Negative_regulation (lacking) of Neg (lacking) Gene_expression (expression) of PrPC
6) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.58 Pain Relevance 0
While we designed this experiment to test RVG-9r LSPC-mediated PrP siRNA delivery to PrPC-expressing neurons, we also observed a significant decrease in PrPC expression on CNS cells after just 24 hours post treatment.
Negative_regulation (decrease) of Gene_expression (expression) of PrPC in neurons
7) Confidence 0.59 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.18 Pain Relevance 0.03
PrP expression was observed to significantly decrease in siRNA-transfected neurons (Fig. 3 D).
Negative_regulation (decrease) of Gene_expression (expression) of PrP in neurons
8) Confidence 0.59 Published 2008 Journal The Journal of Cell Biology Section Body Doc Link PMC2364707 Disease Relevance 0.08 Pain Relevance 0.04
On the the other hand, if the decrease of PrPSc levels by Rab22a-expression was not due to increased PrPSc degradation but rather to inhibition of PrPSc synthesis, NH4Cl treatment should not interfere and we should still observe a decrease in PrPSc levels.
Negative_regulation (inhibition) of Gene_expression (synthesis) of PrPSc
9) Confidence 0.58 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2673690 Disease Relevance 0.07 Pain Relevance 0
Decreasing neuronal PrPC expression in scrapie-infected mice decreases incidence and severity, delays development [11], [12], [13] and can even reverse neuropathology of prion diseases [14].
Negative_regulation (Decreasing) of Gene_expression (expression) of PrPC in neuronal associated with prion diseases and scrapie
10) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 1.74 Pain Relevance 0.10
These data convincingly demonstrate that PrP LSPCs can sufficiently knockdown PrPC expression to decrease prion infection beyond delectability in two distinct cell culture models.


Negative_regulation (decrease) of Gene_expression (expression) of PrPC associated with infection
11) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.41 Pain Relevance 0
To further test this hypothesis and to discriminate between increased degradation and decreased production of PrPSc, we compared the levels of PrPSc in control cells and in cells transfected with GFP-Rab22a after treating them with ammonium chloride (NH4Cl), which impairs lysosomal degradation [43].
Negative_regulation (decreased) of Gene_expression (production) of PrPSc
12) Confidence 0.50 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2673690 Disease Relevance 0.10 Pain Relevance 0
Therefore, under these conditions the reduction in PrPSc was likely due to inhibition of PrPSc production rather than its increased degradation.
Negative_regulation (inhibition) of Gene_expression (production) of PrPSc
13) Confidence 0.50 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2673690 Disease Relevance 0 Pain Relevance 0
These results therefore suggest that the observed reduction of PrPSc levels in GFP-Rab22a expressing cells is due to impaired PrPSc production rather than to increased degradation.


Negative_regulation (impaired) of Gene_expression (production) of PrPSc
14) Confidence 0.50 Published 2009 Journal PLoS Pathogens Section Body Doc Link PMC2673690 Disease Relevance 0.08 Pain Relevance 0
While RVG-9r LSPCs efficiently delivered PrP siRNA to HEK293 cells, they failed to suppress PrPC expression (data not shown).
Neg (failed) Negative_regulation (suppress) of Gene_expression (expression) of PrPC
15) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.11 Pain Relevance 0
Merged images (figures 4d, h, l and p) reveal substantial PrPC expression in all treatment groups except N2a cells treated with RVG-9r-PrP siRNA-containing LSPCs, where PrPC expression appeared significantly diminished, especially on cells with Alexa 488-labeled PrP siRNA still evident (figures 4m–p).FACS analysis of treated cells indicates reduced expression of PrPC on cells treated with PrP-RVG-9r LSPCs, with little or no change in PrPC expression on cells treated with PrP-RVM-9r LSPCs, control-RVG-9r LSPCs or liposomes alone (figure 4q).
Negative_regulation (diminished) of Gene_expression (expression) of PrPC
16) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0 Pain Relevance 0
Taken together, these data demonstrate effective delivery of siRNA to N2a cells using RVG-9r LSPCs and specific suppression of murine PrPC expression when these LSPCs delivered PrP siRNA.


Negative_regulation (suppression) of Gene_expression (expression) of PrPC
17) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.40 Pain Relevance 0
We envision LSPC therapy to be a new delivery system that greatly enhances the capacity of PrP siRNA to transiently suppress PrPC expression in nearly every neuron in the CNS that will significantly impede prion replication and disease progression.
Negative_regulation (suppress) of Gene_expression (expression) of PrPC in neuron associated with disease progression
18) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.69 Pain Relevance 0.03
Recent advances toward an effective therapy for prion diseases employ RNA interference to suppress PrPC expression and subsequent prion neuropathology, exploiting the phenomenon that disease severity and progression correlate with host PrPC expression levels.
Negative_regulation (suppress) of Gene_expression (expression) of PrPC associated with prion diseases and disease
19) Confidence 0.43 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2885418 Disease Relevance 0.20 Pain Relevance 0
3) reduced PrPC expression to approximately 75±11% (figure 6y) relative to all control groups combined (p<0.05, n?
Negative_regulation (reduced) of Gene_expression (expression) of PrPC
20) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2885418 Disease Relevance 0.14 Pain Relevance 0

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