INT99262

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Context Info
Confidence 0.31
First Reported 2001
Last Reported 2008
Negated 0
Speculated 0
Reported most in Abstract
Documents 16
Total Number 16
Disease Relevance 9.99
Pain Relevance 7.38

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

molecular_function (Defb42) cellular_component (Defb42) biological_process (Defb42)
Anatomy Link Frequency
brain 2
Defb42 (Mus musculus)
Pain Link Frequency Relevance Heat
cINOD 77 99.74 Very High Very High Very High
Abeta 40 99.16 Very High Very High Very High
Inflammation 7 95.28 Very High Very High Very High
Inflammatory response 2 92.56 High High
diclofenac 3 92.04 High High
aspirin 3 90.52 High High
agonist 1 78.40 Quite High
Disease Link Frequency Relevance Heat
Alzheimer's Dementia 63 100.00 Very High Very High Very High
Amyloid Plaque 6 98.96 Very High Very High Very High
Targeted Disruption 10 98.88 Very High Very High Very High
Disease 35 98.08 Very High Very High Very High
INFLAMMATION 24 95.28 Very High Very High Very High
Toxicity 6 92.56 High High
Disease Progression 1 75.60 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The inhibition of Abeta42 production is independent from the anti-cyclooxygenase (COX) activity and is related to the chemical structure of the compounds, with some NSAIDs being active (ibuprofen, sulindac, flurbiprofen, indomethacin, diclofenac) and others not (naproxen, aspirin, celecoxib).
Gene_expression (production) of Abeta42 associated with aspirin, cinod and diclofenac
1) Confidence 0.31 Published 2004 Journal Expert Opin Investig Drugs Section Abstract Doc Link 15500394 Disease Relevance 1.27 Pain Relevance 0.59
More recently it has been shown that some NSAIDs decrease the production of amyloid-beta(1-42) (Abeta42), the major component of senile plaques of the AD brain, and counteract the progression of Abeta42 pathology in transgenic mouse models of AD.
Gene_expression (production) of Abeta42 in brain associated with targeted disruption, alzheimer's dementia, cinod, disease and amyloid plaque
2) Confidence 0.31 Published 2004 Journal Expert Opin Investig Drugs Section Abstract Doc Link 15500394 Disease Relevance 1.17 Pain Relevance 0.52
This could explain the negative results of the large AD trials carried out so far, as they were conducted with compounds (naproxen, hydroxychloroquine, dapsone, prednisone, rofecoxib and celecoxib) that are not able to decrease Abeta42 production.
Gene_expression (production) of Abeta42 associated with disease
3) Confidence 0.31 Published 2004 Journal Expert Opin Investig Drugs Section Abstract Doc Link 15500394 Disease Relevance 1.15 Pain Relevance 0.64
This benefit may be partially attributable to the ability of NSAIDs to selectively reduce production of the amyloidogenic A beta 42 peptide in both cultured cells and transgenic mice.
Gene_expression (production) of beta 42 peptide associated with targeted disruption and cinod
4) Confidence 0.24 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12805355 Disease Relevance 0.72 Pain Relevance 0.67
These compounds seem to target the gamma-secretase complex, increasing gamma-secretase-catalyzed production of Abeta42 in vitro.
Gene_expression (production) of Abeta42
5) Confidence 0.13 Published 2005 Journal Nat. Med. Section Abstract Doc Link 15834426 Disease Relevance 0.31 Pain Relevance 0.27
The elevations in Abeta42 by these compounds are comparable to the increases in Abeta42 induced by Alzheimer disease-causing mutations in the genes encoding amyloid beta protein precursor and presenilins, raising the possibility that exogenous compounds or naturally occurring isoprenoids might increase Abeta42 production in humans.
Gene_expression (production) of Abeta42 associated with alzheimer's dementia
6) Confidence 0.13 Published 2005 Journal Nat. Med. Section Abstract Doc Link 15834426 Disease Relevance 0.33 Pain Relevance 0.21
Increased Abeta42 production has been linked to the development of Alzheimer disease.
Gene_expression (production) of Abeta42 associated with alzheimer's dementia
7) Confidence 0.13 Published 2005 Journal Nat. Med. Section Abstract Doc Link 15834426 Disease Relevance 0.17 Pain Relevance 0.23
Diverse compounds mimic Alzheimer disease-causing mutations by augmenting Abeta42 production.
Gene_expression (production) of Abeta42 associated with alzheimer's dementia
8) Confidence 0.13 Published 2005 Journal Nat. Med. Section Title Doc Link 15834426 Disease Relevance 0.33 Pain Relevance 0.26
Compounds devoid of COX activity and the endogenous isoprenoids FPP and GGPP also raised Abeta42.
Gene_expression (raised) of Abeta42
9) Confidence 0.12 Published 2005 Journal Nat. Med. Section Abstract Doc Link 15834426 Disease Relevance 0.30 Pain Relevance 0.28
Short-term in vivo studies show that two Abeta42-raising compounds increase Abeta42 levels in the brains of mice.
Gene_expression (levels) of Abeta42 in brains
10) Confidence 0.12 Published 2005 Journal Nat. Med. Section Abstract Doc Link 15834426 Disease Relevance 0.33 Pain Relevance 0.25
Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Abeta42 peptide (the 42-residue isoform of the amyloid-beta peptide) produced from a variety of cultured cells by as much as 80%.
Gene_expression (produced) of Abeta42 associated with alzheimer's dementia and cinod
11) Confidence 0.10 Published 2001 Journal Nature Section Abstract Doc Link 11700559 Disease Relevance 0.44 Pain Relevance 0.75
We found that Rho and its effector, Rho-associated kinase, preferentially regulated the amount of Abeta42 produced in vitro and that only those NSAIDs effective as Rho inhibitors lowered Abeta42.
Gene_expression (produced) of Abeta42 associated with cinod
12) Confidence 0.05 Published 2003 Journal Science Section Abstract Doc Link 14615541 Disease Relevance 0.50 Pain Relevance 0.43
While some NSAIDs may inhibit Abeta42 production, these observations suggest that ibuprofen reduction of Abeta pathology may not be mediated by altered Abeta42 production.
Gene_expression (production) of Abeta42 associated with cinod and abeta
13) Confidence 0.01 Published 2005 Journal Neuropsychopharmacology Section Abstract Doc Link 15688088 Disease Relevance 0.62 Pain Relevance 0.63
While some NSAIDs may inhibit Abeta42 production, these observations suggest that ibuprofen reduction of Abeta pathology may not be mediated by altered Abeta42 production.
Gene_expression (production) of Abeta42 associated with cinod and abeta
14) Confidence 0.01 Published 2005 Journal Neuropsychopharmacology Section Abstract Doc Link 15688088 Disease Relevance 0.58 Pain Relevance 0.59
In vitro studies using APP-expressing 293 cells showed that ibuprofen directly affected APP processing, specifically reducing the production of Abeta42.
Gene_expression (production) of Abeta42
15) Confidence 0.01 Published 2003 Journal J. Neurosci. Section Abstract Doc Link 12930788 Disease Relevance 1.05 Pain Relevance 0.68
Generation of Abeta38 and Abeta42 is independently and differentially affected by familial Alzheimer disease-associated presenilin mutations and gamma-secretase modulation.
Gene_expression (Generation) of Abeta42 associated with alzheimer's dementia
16) Confidence 0.00 Published 2008 Journal J. Biol. Chem. Section Title Doc Link 17962197 Disease Relevance 0.70 Pain Relevance 0.37

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