INT126200

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Context Info
Confidence 0.58
First Reported 2005
Last Reported 2011
Negated 1
Speculated 15
Reported most in Body
Documents 73
Total Number 89
Disease Relevance 50.19
Pain Relevance 7.44

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

endosome (Bace1) peptidase activity (Bace1) Golgi apparatus (Bace1)
endoplasmic reticulum (Bace1) enzyme binding (Bace1)
Anatomy Link Frequency
brains 6
neuronal 2
neurons 2
cleavage 2
plaque 2
Bace1 (Mus musculus)
Pain Link Frequency Relevance Heat
antagonist 100 100.00 Very High Very High Very High
agonist 124 99.86 Very High Very High Very High
Hippocampus 301 99.82 Very High Very High Very High
Inflammatory marker 2 99.22 Very High Very High Very High
cINOD 423 98.96 Very High Very High Very High
Neuronal excitability 65 98.44 Very High Very High Very High
cytokine 248 98.32 Very High Very High Very High
Peripheral nervous system 257 97.56 Very High Very High Very High
Central nervous system 298 97.24 Very High Very High Very High
potassium channel 53 96.12 Very High Very High Very High
Disease Link Frequency Relevance Heat
Repression 59 100.00 Very High Very High Very High
Alzheimer's Dementia 2059 99.96 Very High Very High Very High
Disease 6251 99.84 Very High Very High Very High
Targeted Disruption 2415 99.66 Very High Very High Very High
Cognitive Disorder 1128 99.20 Very High Very High Very High
Immunization 39 99.08 Very High Very High Very High
INFLAMMATION 1143 99.06 Very High Very High Very High
Convulsion 206 99.00 Very High Very High Very High
Stress 1512 98.68 Very High Very High Very High
Schizophrenia 10 98.04 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
generation in the brains of BACE1 deficient mice indicates that therapeutic inhibition of BACE1 should reduce cerebral A?
Negative_regulation (inhibition) of BACE1 in brains
1) Confidence 0.58 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 0.80 Pain Relevance 0
production, and it is highly likely that a partial inhibition of BACE1 activity may be beneficial, although the percentage of BACE1 inhibition required to significantly delay amyloid pathology and the associated cognitive changes requires further determination.
Spec (partial) Negative_regulation (inhibition) of BACE1 associated with cognitive disorder and alzheimer's dementia
2) Confidence 0.58 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 0.93 Pain Relevance 0
However, given that AICD may be required for normal memory, the degree of BACE1 inhibition required to have beneficial lowering effects on A?
Negative_regulation (inhibition) of BACE1
3) Confidence 0.58 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 0.75 Pain Relevance 0
Interestingly, ibuprofen (and pioglitazone) treatment appeared to decrease BACE1 and reduce plaque load [197].
Negative_regulation (decrease) of BACE1 in plaque
4) Confidence 0.58 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 1.30 Pain Relevance 0.42
-secretase activity was decreased in AD temporal lobe tissue derived from LOAD patients [135].
Negative_regulation (decreased) of secretase in temporal lobe associated with disease
5) Confidence 0.58 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 0.70 Pain Relevance 0
generation in the brains of BACE1 deficient mice indicates that therapeutic inhibition of BACE1 should reduce cerebral A?
Negative_regulation (inhibition) of BACE1 in brains
6) Confidence 0.58 Published 2007 Journal Mol Neurodegener Section Body Doc Link PMC2211305 Disease Relevance 0.65 Pain Relevance 0
Although further work is required, these data indicate that a partial suppression of BACE1 may have the most benefit for the earlier phases of A?
Spec (partial) Negative_regulation (suppression) of BACE1
7) Confidence 0.58 Published 2007 Journal Mol Neurodegener Section Body Doc Link PMC2211305 Disease Relevance 0.50 Pain Relevance 0
agonists cause repression of BACE1 gene promoter activity, while proinflammatory cytokines that reduce PPAR?
Negative_regulation (repression) of BACE1 gene associated with repression, agonist and cytokine
8) Confidence 0.58 Published 2007 Journal Mol Neurodegener Section Body Doc Link PMC2211305 Disease Relevance 0.60 Pain Relevance 0.63
Early on, data indicated that BACE knockout mice were phenotypically normal although more recent, detailed analyses show that complete abolishment of BACE1 activity may have potentially deleterious effects.
Negative_regulation (abolishment) of BACE1 associated with targeted disruption
9) Confidence 0.58 Published 2007 Journal Mol Neurodegener Section Body Doc Link PMC2211305 Disease Relevance 0.54 Pain Relevance 0
-secretase activity is abolished in brains and cultured neurons of BACE1-/- mice.
Negative_regulation (abolished) of secretase in brains
10) Confidence 0.58 Published 2007 Journal Mol Neurodegener Section Body Doc Link PMC2211305 Disease Relevance 0.45 Pain Relevance 0
In parallel to the suppression of inflammatory markers, pioglitazone and ibuprofen treatment decreased beta-secretase-1 (BACE1) mRNA and protein levels.
Negative_regulation (decreased) of BACE1 associated with inflammatory marker
11) Confidence 0.56 Published 2005 Journal Brain Section Abstract Doc Link 15817521 Disease Relevance 0.77 Pain Relevance 0.83
In parallel to the suppression of inflammatory markers, pioglitazone and ibuprofen treatment decreased beta-secretase-1 (BACE1) mRNA and protein levels.
Negative_regulation (decreased) of beta-secretase-1 associated with inflammatory marker
12) Confidence 0.56 Published 2005 Journal Brain Section Abstract Doc Link 15817521 Disease Relevance 0.76 Pain Relevance 0.83
In particular, the larger active site of BACE1 renders it extremely difficult to inhibit this aspartic protease with small-molecule compounds that can pass the blood-brain barrier.
Negative_regulation (inhibit) of aspartic protease in brain
13) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944882 Disease Relevance 0.92 Pain Relevance 0
can limit the abilities of partial BACE1 reduction to suppress A?
Spec (partial) Negative_regulation (reduction) of BACE1
14) Confidence 0.51 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944882 Disease Relevance 0.15 Pain Relevance 0
Despite the apparent benefits of a reduction in BACE1 levels reported above, there has been a recent study that contains data that may be a cause for some concern.
Negative_regulation (reduction) of BACE1
15) Confidence 0.50 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 0.25 Pain Relevance 0
Interestingly, Singer and colleagues demonstrated that a partial reduction in BACE1 can improve amyloid neuropathology including the deposition of A?
Spec (partial) Negative_regulation (reduction) of BACE1 associated with alzheimer's dementia
16) Confidence 0.50 Published 2007 Journal Current Genomics Section Body Doc Link PMC2647160 Disease Relevance 0.52 Pain Relevance 0
Interestingly, Singer and colleagues used RNA interference (RNAi) to silence BACE1 and demonstrated that a partial reduction in BACE1 can improve amyloid neuropathology including the deposition of A?
Spec (partial) Negative_regulation (reduction) of BACE1 associated with alzheimer's dementia
17) Confidence 0.50 Published 2007 Journal Mol Neurodegener Section Body Doc Link PMC2211305 Disease Relevance 0.52 Pain Relevance 0.07
production is not required for functional improvements, it has not been examined whether the beneficial effects of partial BACE1 suppression may remain unchanged during highly advanced stages of AD.
Spec (partial) Negative_regulation (suppression) of BACE1 associated with disease
18) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944882 Disease Relevance 0.53 Pain Relevance 0.03
levels following systemic administration of future BACE1 inhibitor drugs may be limited [16], [17], it is important to determine the degree of BACE1 suppression that is required to exert therapeutic benefits including memory improvements during the progression of AD.
Negative_regulation (suppression) of BACE1 associated with disease
19) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944882 Disease Relevance 0.89 Pain Relevance 0
A better understanding of the consequences of BACE1 deficiency will aid in the design of therapeutic strategies to abrogate A?
Negative_regulation (deficiency) of BACE1
20) Confidence 0.43 Published 2010 Journal Mol Neurodegener Section Body Doc Link PMC2933677 Disease Relevance 0.55 Pain Relevance 0.26

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