INT3622

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Context Info
Confidence 0.58
First Reported 1976
Last Reported 2010
Negated 4
Speculated 1
Reported most in Abstract
Documents 34
Total Number 35
Disease Relevance 16.08
Pain Relevance 8.76

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

peptidase activity (CTSB) mitochondrion (CTSB) extracellular space (CTSB)
extracellular region (CTSB) intracellular (CTSB) lysosome (CTSB)
Anatomy Link Frequency
cleavage 5
HeLa 2
D22 1
macrophage 1
brain 1
CTSB (Homo sapiens)
Pain Link Frequency Relevance Heat
Neurotransmitter 3 99.84 Very High Very High Very High
cINOD 90 99.74 Very High Very High Very High
Abeta 57 99.60 Very High Very High Very High
Analgesic 2 97.10 Very High Very High Very High
Inflammation 12 95.68 Very High Very High Very High
Potency 4 88.60 High High
anesthesia 1 79.36 Quite High
monoamine 1 79.32 Quite High
diclofenac 2 78.64 Quite High
Chronic pancreatitis 6 70.76 Quite High
Disease Link Frequency Relevance Heat
American Trypanosomiasis 36 100.00 Very High Very High Very High
Alzheimer's Dementia 69 99.80 Very High Very High Very High
Brain Disease 2 99.72 Very High Very High Very High
INFLAMMATION 41 99.42 Very High Very High Very High
Disease 172 99.12 Very High Very High Very High
Coronary Heart Disease 12 98.56 Very High Very High Very High
Toxicity 17 97.84 Very High Very High Very High
Apoptosis 1 96.92 Very High Very High Very High
Pancreatitis 46 90.12 High High
Congenital Anomalies 6 87.24 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Analgesics, antimalarials, cytostatic agents, steroids as well as d-penicillamine, colchicine, allopurinol, chlorzoxazone and chlorpromazine either had no effect on cathepsin B1 or inhibited it to a very small extent.
Neg (no) Regulation (effect) of cathepsin B1 associated with analgesic
1) Confidence 0.58 Published 1976 Journal Z Rheumatol Section Abstract Doc Link 817531 Disease Relevance 0.10 Pain Relevance 0.18
Long-term histopathological and behavioral animal studies are available with these NSAIDs (mainly ibuprofen) but it is unclear if the observed in vivo effects on Abeta brain pathology and learning depend on their activity on gamma-secretase or on other biological targets.
Regulation (depend) of gamma-secretase in brain associated with brain disease, cinod and abeta
2) Confidence 0.50 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.79 Pain Relevance 0.53
Interestingly, some non-steroidal anti-inflammatory drugs (NSAIDs) and other small organic molecules have been found to modulate gamma-secretase and to selectively reduce beta-amyloid(1-42) (Abeta42) levels without affecting Notch cleavage.
Regulation (modulate) of gamma-secretase in cleavage associated with inflammation, alzheimer's dementia and cinod
3) Confidence 0.50 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220933 Disease Relevance 0.91 Pain Relevance 0.52
This indicates a high control of cathepsin B action on trypsinogen activation by the amino acid structure of TAP and highlights the particular functional importance of the D22 residue within the tetraaspartic group D19-D20-D21-D22.
Regulation (action) of cathepsin B in D22
4) Confidence 0.41 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.18 Pain Relevance 0
In contrast to the mutations N29I, N29T and R122H, which are located away from this cleavage site, trypsinogen mutations affecting the K23-I24 bond could potentially affect the cathepsin B action on trypsinogen activation.
Regulation (affect) of cathepsin B in cleavage
5) Confidence 0.30 Published 2002 Journal BMC Gastroenterol Section Body Doc Link PMC117221 Disease Relevance 0.29 Pain Relevance 0.07
His research on the neuropathogenesis of Alzheimer's disease has focused primarily on the molecular mechanisms underlying beta-amyloid precursor protein processing and beta-amyloid protein production, especially regarding regulation of the gamma-secretase complex.Additionally, his work has addressed the role of presenilin-related apoptosis in Alzheimer's disease.
Regulation (regulation) of gamma-secretase associated with alzheimer's dementia, apoptosis and disease
6) Confidence 0.25 Published 2005 Journal J. Mol. Neurosci. Section Abstract Doc Link 15781967 Disease Relevance 0.66 Pain Relevance 0.08
Effect of antirheumatic drugs on cathepsin B1 from bovine spleen.
Regulation (Effect) of cathepsin B1 in spleen
7) Confidence 0.25 Published 1976 Journal Z Rheumatol Section Title Doc Link 817531 Disease Relevance 0.08 Pain Relevance 0.16
A straightforward explanation of this failure is that the gamma-secretase is not the right target for therapy or that, in general, blocking A beta does not produce clinical benefits in AD.
Neg (not) Regulation (target) of gamma-secretase associated with disease
8) Confidence 0.22 Published 2009 Journal J. Alzheimers Dis. Section Abstract Doc Link 19542625 Disease Relevance 0.82 Pain Relevance 0.10
There has been a lot of disappointment surrounding the recent failure of the largest ever study in patients with Alzheimer's disease (AD) with tarenflurbil, a compound believed to modulate the activity of gamma-secretase, the pivotal enzyme that generates the amyloid-beta (A beta) peptide from the amyloid-beta protein precursor.
Regulation (modulate) of gamma-secretase associated with alzheimer's dementia and disease
9) Confidence 0.22 Published 2009 Journal J. Alzheimers Dis. Section Abstract Doc Link 19542625 Disease Relevance 0.60 Pain Relevance 0
Our data suggest that SSide is a direct inhibitor of gamma-secretase that preferentially affects the gamma(42)-secretase activity.
Regulation (affects) of secretase
10) Confidence 0.19 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.26 Pain Relevance 0.37
Gamma-secretase modulation and its promise for Alzheimer's disease: a medicinal chemistry perspective.
Regulation (modulation) of Gamma-secretase associated with disease
11) Confidence 0.16 Published 2008 Journal Curr Top Med Chem Section Title Doc Link 18220931 Disease Relevance 0.60 Pain Relevance 0.32
In addition, a very limited number of non-NSAID derived gamma secretase modulators has also been recently claimed in the patent literature, suggesting that only a restricted number of pharmacophores might be involved in the modulation of gamma-secretase.
Regulation (modulation) of gamma-secretase associated with cinod
12) Confidence 0.16 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220931 Disease Relevance 0.51 Pain Relevance 0.39
Gamma-secretase modulation holds the promise for the development of a disease-modifying therapy for Alzheimer's disease (AD).
Regulation (modulation) of Gamma-secretase associated with disease
13) Confidence 0.16 Published 2008 Journal Curr Top Med Chem Section Abstract Doc Link 18220931 Disease Relevance 0.49 Pain Relevance 0.12
Selected non-steroidal anti-inflammatory drugs and their derivatives target gamma-secretase at a novel site.
Regulation (target) of gamma-secretase associated with inflammation and cinod
14) Confidence 0.09 Published 2004 Journal J. Biol. Chem. Section Title Doc Link 15304503 Disease Relevance 0.53 Pain Relevance 0.40
Here we show that sulindac sulfide (SSide) directly acts on gamma-secretase and preferentially inhibits the gamma(42)-secretase activity derived from the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate-solubilized membrane fractions of HeLa cells, in an in vitro gamma-secretase assay using recombinant amyloid beta precursor protein C100 as a substrate.
Regulation (acts) of secretase in HeLa associated with alzheimer's dementia
15) Confidence 0.08 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.34 Pain Relevance 0.51
Here we show that sulindac sulfide (SSide) directly acts on gamma-secretase and preferentially inhibits the gamma(42)-secretase activity derived from the 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propanesulfonate-solubilized membrane fractions of HeLa cells, in an in vitro gamma-secretase assay using recombinant amyloid beta precursor protein C100 as a substrate.
Regulation (acts) of secretase in HeLa associated with alzheimer's dementia
16) Confidence 0.08 Published 2003 Journal J. Biol. Chem. Section Abstract Doc Link 12637581 Disease Relevance 0.34 Pain Relevance 0.51
Additionally, ALDH3A1, CRP, and HPT were induced by BaP subacute treatment, whereas another type of ALDH inducer, phenobarbital, did not affect the levels of APPs or ALDH3A1, but did increase ALDH1A3 activity.
Neg (not) Regulation (affect) of APPs
17) Confidence 0.06 Published 2003 Journal Chem. Biol. Interact. Section Abstract Doc Link 12604189 Disease Relevance 0.09 Pain Relevance 0.21
Recent strategies avoid this problem, as in the case of some nonsteroidal anti-inflammatory drugs (NSAIDs) which do not alter secretase activity but alter its cleavage site specificity resulting in the generation of the less toxic 38 residue A?
Neg (not) Regulation (alter) of secretase in cleavage associated with inflammation and cinod
18) Confidence 0.05 Published 2010 Journal International Journal of Alzheimer's Disease Section Body Doc Link PMC2915753 Disease Relevance 0.49 Pain Relevance 0.20
We and others previously showed that both the synthesis of the amyloid precursor protein (APP) and its processing (i.e., to amyloidogenic A beta peptides; soluble nonamyloidogenic APPs; and other APP fragments) are regulated by neurotransmitters.
Regulation (regulated) of APPs associated with neurotransmitter and alzheimer's dementia
19) Confidence 0.04 Published 2000 Journal Ann. N. Y. Acad. Sci. Section Abstract Doc Link 11193162 Disease Relevance 0.10 Pain Relevance 0.11
Gamma-secretase modulation with Abeta42-lowering nonsteroidal anti-inflammatory drugs and derived compounds.
Regulation (modulation) of Gamma-secretase associated with inflammation and cinod
20) Confidence 0.04 Published 2006 Journal Neurodegener Dis Section Title Doc Link 17047371 Disease Relevance 0.80 Pain Relevance 0.34

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