INT84932

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Context Info
Confidence 0.57
First Reported 1999
Last Reported 2010
Negated 2
Speculated 0
Reported most in Abstract
Documents 29
Total Number 29
Disease Relevance 28.45
Pain Relevance 7.20

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 (APP) extracellular matrix organization (APP) DNA binding (APP)
cytoplasm (APP) cytosol (APP) extracellular region (APP)
Anatomy Link Frequency
brain 3
plasma 2
neurite 1
APP (Homo sapiens)
Pain Link Frequency Relevance Heat
Abeta 96 100.00 Very High Very High Very High
cINOD 93 99.22 Very High Very High Very High
nociceptor 11 98.40 Very High Very High Very High
Pain 26 97.80 Very High Very High Very High
Eae 9 96.56 Very High Very High Very High
Glutamate 2 92.96 High High
Multiple sclerosis 6 92.80 High High
Central nervous system 47 91.72 High High
Hippocampus 23 91.48 High High
cerebral cortex 2 90.96 High High
Disease Link Frequency Relevance Heat
Alzheimer's Dementia 403 100.00 Very High Very High Very High
Targeted Disruption 72 100.00 Very High Very High Very High
Lyme Neuroborreliosis 265 99.86 Very High Very High Very High
Disease 525 99.84 Very High Very High Very High
Pheochromocytoma 2 99.68 Very High Very High Very High
Infection 33 99.60 Very High Very High Very High
Parkinson's Disease 6 99.32 Very High Very High Very High
Acute Disease 10 99.28 Very High Very High Very High
Systemic Lupus Erythematosus 25 99.20 Very High Very High Very High
Cognitive Disorder 117 99.16 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We found that overexpression of OSBP1 in cells stably expressing APP led to downregulation of the amyloidogenic processing shown by a decrease in APP-CTF?
Negative_regulation (decrease) of APP
1) Confidence 0.57 Published 2008 Journal Mol Neurodegener Section Body Doc Link PMC2323375 Disease Relevance 0.13 Pain Relevance 0
The first published clinical studies in healthy subjects and in AD patients with a gamma-secretase inhibitor, LY-450139, confirmed the dose-dependent inhibition of plasma Abeta but evidenced a later rebound in Abeta plasma levels and absence of a significant effect on cerebrospinal fluid Abeta concentrations.
Negative_regulation (inhibition) of Abeta in plasma associated with disease and abeta
2) Confidence 0.52 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.58 Pain Relevance 0.52
-sAPP may be generally reduced in diseases with pronounced neuroinflammation.
Negative_regulation (reduced) of sAPP associated with disease
3) Confidence 0.46 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2902447 Disease Relevance 2.18 Pain Relevance 0.24
Novel promising strategies suggest the use of anti-inflammatory drugs, antioxidants including natural occurring plant flavonoids, iron-complexing molecules, neurotrophic factor delivery, inhibitors of the amyloid-beta protein precursor processing secretases, gamma and beta, that generate amyloid-beta peptides and the interference with lipid and cholesterol metabolism.
Negative_regulation (inhibitors) of amyloid-beta associated with inflammation, alzheimer's dementia and cinod
4) Confidence 0.43 Published 2008 Journal J. Alzheimers Dis. Section Abstract Doc Link 18953110 Disease Relevance 0.85 Pain Relevance 0.10
Based on this model, we systematically demonstrated that several classes of organic compounds (e.g., wine-related polyphenols, non-steroidal anti-inflammatory drugs) not only inhibit the formation of Abeta amyloid fibrils from Abeta and their extension, but also destabilize Abeta amyloid fibrils dose-dependently in vitro.
Negative_regulation (destabilize) of Abeta associated with inflammation, alzheimer's dementia, cinod and abeta
5) Confidence 0.43 Published 2010 Journal Yakugaku Zasshi Section Abstract Doc Link 20371993 Disease Relevance 0.59 Pain Relevance 0.35
We demonstrate that treatment with dox suppresses steady-state levels of both APPswe/ind and its C-terminal fragments, indicating that the mutant proteins have a relatively short half-life in vivo.
Negative_regulation (suppresses) of APP
6) Confidence 0.42 Published 2005 Journal PLoS Medicine Section Body Doc Link PMC1283364 Disease Relevance 0.85 Pain Relevance 0.04
Nonsteroidal anti-inflammatory drugs, which inhibit the activity of COX-1 and COX-2, decrease AAA expansion in humans and animal models of the disease.
Negative_regulation (decrease) of AAA associated with inflammation and disease
7) Confidence 0.42 Published 2006 Journal Arterioscler. Thromb. Vasc. Biol. Section Abstract Doc Link 16514081 Disease Relevance 0.45 Pain Relevance 0.18
Angiographic myocardial blush grade, corrected TIMI frame count (CTFC) and reduction in ST segment elevation were used as markers of myocardial reperfusion.
Negative_regulation (reduction) of CTFC
8) Confidence 0.42 Published 2008 Journal Current Cardiology Reviews Section Body Doc Link PMC2801861 Disease Relevance 0 Pain Relevance 0
Extracellular deposition of amyloid beta-peptide (Abeta) has been implicated as a critical step in the pathogenesis of AD.
Negative_regulation (deposition) of Abeta associated with alzheimer's dementia, disease and abeta
9) Confidence 0.41 Published 2008 Journal Curr. Pharm. Des. Section Abstract Doc Link 19075706 Disease Relevance 1.89 Pain Relevance 0.54
We report an association of cerebral amyloid metabolism with LNB, with decreased CSF levels of soluble APP-fragments in the acute disease stage.
Negative_regulation (decreased) of APP associated with acute disease, lyme neuroborreliosis and alzheimer's dementia
10) Confidence 0.39 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2902447 Disease Relevance 1.52 Pain Relevance 0.12
Gamma-secretase modulators (GSMs) include selected non-steroidal anti-inflammatory drugs such as flurbiprofen that selectively lowers the neurotoxic amyloid-beta peptide Abeta(1-42).
Negative_regulation (lowers) of amyloid-beta associated with inflammation, alzheimer's dementia, cinod and abeta
11) Confidence 0.38 Published 2009 Journal J. Neurochem. Section Abstract Doc Link 19702658 Disease Relevance 0.52 Pain Relevance 0.50
Gamma-secretase modulators (GSMs) include selected non-steroidal anti-inflammatory drugs such as flurbiprofen that selectively lowers the neurotoxic amyloid-beta peptide Abeta(1-42).
Negative_regulation (lowers) of Abeta associated with inflammation, alzheimer's dementia, cinod and abeta
12) Confidence 0.38 Published 2009 Journal J. Neurochem. Section Abstract Doc Link 19702658 Disease Relevance 0.52 Pain Relevance 0.51
We found significant positive correlations of the effective concentrations (EC(50)) of these compounds ranging from 10 nM to 10 microM, for the formation and destabilization of Abeta amyloid fibrils.
Negative_regulation (destabilization) of Abeta associated with alzheimer's dementia and abeta
13) Confidence 0.38 Published 2010 Journal Yakugaku Zasshi Section Abstract Doc Link 20371993 Disease Relevance 0.61 Pain Relevance 0.39
Consistent with the high cholesterol content of the CNS, OSBP1 and many ORPs are highly expressed in several brain regions [30,31], and we recently demonstrated that oxysterols can inhibit APP processing [32].
Negative_regulation (inhibit) of APP in brain
14) Confidence 0.37 Published 2008 Journal Mol Neurodegener Section Body Doc Link PMC2323375 Disease Relevance 0 Pain Relevance 0
Development of APP/PS1 Stable Cell Lines
Negative_regulation (Development) of APP
15) Confidence 0.35 Published 2008 Journal Mol Neurodegener Section Body Doc Link PMC2405781 Disease Relevance 0 Pain Relevance 0
-sAPP and P-tau are decreased in acute infection and increase after treatment.
Negative_regulation (decreased) of sAPP associated with infection
16) Confidence 0.34 Published 2010 Journal BMC Neurol Section Abstract Doc Link PMC2902447 Disease Relevance 1.75 Pain Relevance 0.05
-sAPP are reduced in MS and cerebral systemic lupus erythematosus SLE [3], and even lower levels are seen in HIV patients with cerebral engagement [4].
Negative_regulation (reduced) of sAPP associated with acquired immune deficiency syndrome or hiv infection and systemic lupus erythematosus
17) Confidence 0.34 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2902447 Disease Relevance 1.38 Pain Relevance 0.15
-sAPP were decreased in the acute stage of the disease, and increased following treatment with antibiotics.
Negative_regulation (decreased) of sAPP associated with disease
18) Confidence 0.34 Published 2010 Journal BMC Neurol Section Body Doc Link PMC2902447 Disease Relevance 1.56 Pain Relevance 0.12
Given the uncertain Abeta reduction target and the potential for mechanism-based toxicity, it has been suggested that biomarkers for efficacy (cerebrospinal fluid Abeta42 levels) and toxicity (plasma adipsin levels) would be helpful in initial clinical trials with gamma-secretase inhibitors.
Negative_regulation (reduction) of Abeta in plasma associated with toxicity and abeta
19) Confidence 0.33 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.46 Pain Relevance 0.40
Conduction block of the Abeta fibers resulted in an increase in mechanically evoked pain estimates and an increase in temporal summation, consistent with loss of Abeta-mediated inhibition.
Negative_regulation (block) of Abeta associated with pain and abeta
20) Confidence 0.32 Published 1999 Journal J. Neurophysiol. Section Abstract Doc Link 10561433 Disease Relevance 0.56 Pain Relevance 1.16

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