INT193936

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Context Info
Confidence 0.58
First Reported 2006
Last Reported 2009
Negated 1
Speculated 0
Reported most in Body
Documents 5
Total Number 12
Disease Relevance 11.57
Pain Relevance 2.95

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

mitochondrion (PSEN1) Golgi apparatus (PSEN1) endoplasmic reticulum (PSEN1)
embryo development (PSEN1) peptidase activity (PSEN1) cell death (PSEN1)
Anatomy Link Frequency
fibroblasts 6
PSEN1 (Homo sapiens)
PSEN1 - M146L (7)
Pain Link Frequency Relevance Heat
bradykinin 600 100.00 Very High Very High Very High
Inflammation 162 99.20 Very High Very High Very High
Dismenorea 76 75.92 Quite High
Pain score 20 69.12 Quite High
Pain scale 22 68.64 Quite High
nud 10 66.72 Quite High
Pain 150 65.84 Quite High
cINOD 10 45.84 Quite Low
Eae 25 5.00 Very Low Very Low Very Low
imagery 24 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Disease 1616 100.00 Very High Very High Very High
Stress 817 100.00 Very High Very High Very High
INFLAMMATION 163 99.20 Very High Very High Very High
Reprotox - General 1 12 97.88 Very High Very High Very High
Adverse Drug Reaction 12 97.38 Very High Very High Very High
Gastrointestinal Disease 4 97.08 Very High Very High Very High
Apoptosis 197 95.88 Very High Very High Very High
Down Syndrome 128 95.72 Very High Very High Very High
Congenital Anomalies 2 95.68 Very High Very High Very High
Targeted Disruption 19 94.36 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Bradykinin stimulation of PS-1 (M146L) AD fibroblasts results in decreased MAPK activation relative to control fibroblasts
Positive_regulation (stimulation) of PS-1 (M146L) in fibroblasts associated with disease and bradykinin
1) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 0.62 Pain Relevance 0.08
Compound E at 1 nM or 10 nM corrected the deficit in BK-stimulated ERK activation in the PS-1 (M146L) AD fibroblasts, significantly boosting BK-induced ERK activation by 2 fold, as compared to the vehicle only treatment.
Positive_regulation (activation) of PS-1 (M146L) in fibroblasts associated with disease and bradykinin
2) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 0.83 Pain Relevance 0.48
We postulated that the enhanced magnitude of JNK activation in PS-1 (M146L) AD fibroblasts might be a potential mechanistic link to the enhanced oxidative stress-induced apoptosis in these cells relative to normal fibroblasts.
Positive_regulation (activation) of PS-1 (M146L) in fibroblasts associated with stress, apoptosis and disease
3) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 1.90 Pain Relevance 0
However, complementation of FAD-associated variants of PS2 selectively elevated A?
Positive_regulation (variants) of FAD associated with disease
4) Confidence 0.49 Published 2006 Journal Mol Neurodegener Section Body Doc Link PMC1513131 Disease Relevance 0.91 Pain Relevance 0
Hence the diminished BK-induced PS-1 ERK phenotype correctable by gamma-secretase inhibitor Compound E may reflect functional differences in the catalytic core of the gamma-secretase complex generating aspartyl protease activity unique to PS-1 as opposed to PS-2 [38], [41], [56], [57], [63], [64], or alternatively in ER Ca2+ metabolism [41], [65], [66].
Positive_regulation (induced) of PS-1 associated with bradykinin
5) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 0.53 Pain Relevance 0.32
However, ERK displayed a lag in the onset and a reduced magnitude and duration of activation in PS-1 M146L AD fibroblasts stimulated with BK, compared to the activation response of normal control fibroblasts.
Positive_regulation (activation) of PS-1 (M146L) in fibroblasts associated with disease and bradykinin
6) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 0.65 Pain Relevance 0.27
Gamma-secretase inhibitor Compound E restores normal BK-dependent ERK activation in PS-1 (M146L) AD fibroblasts
Positive_regulation (activation) of PS-1 (M146L) in fibroblasts associated with disease and bradykinin
7) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 0.96 Pain Relevance 0.48
Since inflammatory stress yielded a diminished BK-induced activation of all three MAPK modules in PS-1 M146L, we initially assumed that oxidative stress would likely have a similar effect.
Positive_regulation (activation) of PS-1 (M146L) associated with stress, inflammation and bradykinin
8) Confidence 0.39 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 1.58 Pain Relevance 0.25
In the PS-1 M146L AD human skin fibroblasts whose aberrant BK signaling was the strongest, oxidative stress induced a massive enhancement of JNK activation concomitant with lagging p38 and ERK activation.
Positive_regulation (induced) of PS-1 (M146L) in fibroblasts associated with stress, disease and bradykinin
9) Confidence 0.36 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2644820 Disease Relevance 1.86 Pain Relevance 0.28
42 production by FAD mutations in presenilins, possibly related to structural changes; and another one related to inhibitor binding to either PS allosteric sites or the cell membrane which would cause structural changes in the preseniln structure to favor A?
Positive_regulation (mutations) of FAD associated with disease
10) Confidence 0.36 Published 2008 Journal Mol Neurodegener Section Body Doc Link PMC2405781 Disease Relevance 0.10 Pain Relevance 0
Adverse reactions or events historically attributed to traditional Chinese medicine, such as inner heat reaction or disturbed menstruation, did not increase in the FAD group compared with the placebo group.
Neg (not) Positive_regulation (increase) of FAD associated with adverse drug reaction
11) Confidence 0.19 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1940310 Disease Relevance 0.66 Pain Relevance 0.26
The increase in the FAD group was only one episode for inner heat reaction, abnormal menses, or gastrointestinal disorder or illness (Table 3).
Positive_regulation (increase) of FAD associated with gastrointestinal disease and reprotox - general 1
12) Confidence 0.18 Published 2007 Journal PLoS ONE Section Body Doc Link PMC1940310 Disease Relevance 0.97 Pain Relevance 0.52

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