INT124371

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Context Info
Confidence 0.55
First Reported 2005
Last Reported 2011
Negated 0
Speculated 5
Reported most in Body
Documents 170
Total Number 188
Disease Relevance 87.92
Pain Relevance 15.51

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

cell differentiation (Gsk3b) carbohydrate metabolic process (Gsk3b) protein complex (Gsk3b)
response to stress (Gsk3b) cytoplasm (Gsk3b) cytosol (Gsk3b)
Anatomy Link Frequency
muscle 5
MEFs 3
neuronal 3
neurons 3
liver 2
Gsk3b (Mus musculus)
Pain Link Frequency Relevance Heat
fluoxetine 68 99.96 Very High Very High Very High
antidepressant 197 99.88 Very High Very High Very High
agonist 195 99.76 Very High Very High Very High
sSRI 76 99.72 Very High Very High Very High
Kinase C 417 99.60 Very High Very High Very High
Serotonin 84 99.26 Very High Very High Very High
depression 488 99.20 Very High Very High Very High
ischemia 55 99.20 Very High Very High Very High
antagonist 140 98.98 Very High Very High Very High
Nerve growth factor 46 98.98 Very High Very High Very High
Disease Link Frequency Relevance Heat
Death 788 99.92 Very High Very High Very High
Disease 4015 99.84 Very High Very High Very High
Obesity 204 99.84 Very High Very High Very High
Apoptosis 568 99.82 Very High Very High Very High
Cancer 870 99.68 Very High Very High Very High
Stomach Cancer 33 99.60 Very High Very High Very High
Affective Disorder 198 99.48 Very High Very High Very High
Parkinson's Disease 1042 99.42 Very High Very High Very High
Targeted Disruption 2937 99.38 Very High Very High Very High
Aggression 208 99.24 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
A final lithium concentration of 20 mM was chosen representing the upper range of GSK3 inhibition, based on the in vitro dose-response curve of GSK3 to lithium, as described with respect to Tau as well as RevErb?
Negative_regulation (inhibition) of GSK3 in upper
1) Confidence 0.55 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0.05 Pain Relevance 0
-null cell line was subtle in the context of this assay, a much more distinctive and exaggerated mPer2 period lengthening phenotype emerged from the additional RNAi-mediated reduction of GSK3?.
Negative_regulation (reduction) of GSK3 in null cell
2) Confidence 0.55 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0.28 Pain Relevance 0
Considering the subset of BPD patients who are non-responsive to lithium, and the fact that circadian abnormalities do not necessarily result in mood disorders [6], and vice versa, the inhibition of GSK3 by lithium in the context of circadian rhythms is hardly a panacea for the therapy of affective mood disorders.
Negative_regulation (inhibition) of GSK3 associated with affective disorder, congenital anomalies and bronchopulmonary dysplasia
3) Confidence 0.55 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0.95 Pain Relevance 0.42
Although Alsterpaullone is a more potent inhibitor of GSK3 than kenpaullone, it has been shown to be less specific and therefore less suitable for cell-based assays [49].
Negative_regulation (inhibitor) of GSK3
4) Confidence 0.55 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0.06 Pain Relevance 0
Selective inhibition of GSK3 by kenpaullone lengthens mPer2 period
Negative_regulation (inhibition) of GSK3
5) Confidence 0.55 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0 Pain Relevance 0
Our findings raise the question of how loss of GSK-3?
Negative_regulation (loss) of GSK-3
6) Confidence 0.53 Published 2009 Journal Mol Brain Section Body Doc Link PMC2785804 Disease Relevance 0 Pain Relevance 0.03
To examine whether the loss of GSK-3?
Spec (examine) Negative_regulation (loss) of GSK-3
7) Confidence 0.53 Published 2009 Journal Mol Brain Section Body Doc Link PMC2785804 Disease Relevance 0.32 Pain Relevance 0
Lithium, the first clinically utilized drug identified to inhibit GSK-3 in a selective manner [39,40] is widely used to augment antipsychotic treatment in patients with schizophrenia [41,42], Alzheimer's Disease [43], Amyotrophic Lateral Sclerosis [44]; and bipolar mood disorders [45-47].
Negative_regulation (inhibit) of GSK-3 in Lateral associated with affective disorder, disease, motor neuron diseases and schizophrenia
8) Confidence 0.53 Published 2009 Journal Mol Brain Section Body Doc Link PMC2785804 Disease Relevance 1.09 Pain Relevance 0.07
A clear reduction in GSK3?
Negative_regulation (reduction) of GSK3
9) Confidence 0.48 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0.07 Pain Relevance 0
KO mice are partly caused by the reduced phosphorylation levels of Akt and GSK3?.
Negative_regulation (reduced) of GSK3 associated with targeted disruption
10) Confidence 0.47 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2956634 Disease Relevance 0.37 Pain Relevance 0.03
Taken together, these results provide new information suggesting that atypical antipsychotics, in addition to mood stabilizers and antidepressants, can inhibit the activity of GSK3.
Negative_regulation (inhibit) of GSK3 associated with antidepressant
11) Confidence 0.43 Published 2007 Journal Int. J. Neuropsychopharmacol. Section Abstract Doc Link 16672106 Disease Relevance 0.30 Pain Relevance 0.33
There are two major pathways by which lithium is known to affect the activities of multiple transcription factors that control gene expression, and both of these pathways involve inhibitory effects on GSK3: lithium can act as a competitive inhibitor of Mg2+, thereby reducing GSK3 activity [14]; lithium also inhibits GSK3 by increasing the inhibitory phosphorylation of a Ser-9 residue in GSK3?
Negative_regulation (reducing) of GSK3
12) Confidence 0.43 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1880853 Disease Relevance 0.11 Pain Relevance 0
Lithium has been reported to exert its neuroprotective effects predominantly by inhibiting apoptosis through inhibition of GSK3?
Negative_regulation (inhibition) of GSK3 associated with apoptosis
13) Confidence 0.43 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1880853 Disease Relevance 0.52 Pain Relevance 0.04
VacA can disrupt other signal transduction pathways; VacA activates p38 MAPK, enhancing production of IL-8 and PGE(2), and PI3K/Akt, suppressing GSK-3beta activity.
Negative_regulation (suppressing) of GSK-3beta
14) Confidence 0.42 Published 2010 Journal Tohoku J. Exp. Med. Section Abstract Doc Link 20046046 Disease Relevance 1.03 Pain Relevance 0.12
IBU-PO (0.01-1 microM) inhibits glycogen-synthase-kinase-3beta (GSK-3beta) and stabilizes cytoplasmic beta-catenin reverting the silencing of the Wnt pathway caused by Abeta-toxicity and GSK-3beta overexpression.
Negative_regulation (inhibits) of GSK-3beta associated with toxicity and abeta
15) Confidence 0.41 Published 2005 Journal Neurobiol. Dis. Section Abstract Doc Link 15649708 Disease Relevance 0.59 Pain Relevance 0.35
In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-3beta pathway, suggesting NAG-1 alters cell survival.
Negative_regulation (inhibition) of GSK-3beta
16) Confidence 0.41 Published 2006 Journal J. Biochem. Mol. Biol. Section Abstract Doc Link 17129398 Disease Relevance 0.87 Pain Relevance 0.07
Lithium, a direct inhibitor of glycogen synthase kinase 3 (GSK3) activity, and a mainstay in BPD therapeutics, has been proposed to target GSK3 as a mechanism of mood stabilization.
Negative_regulation (inhibitor) of GSK3 associated with bronchopulmonary dysplasia
17) Confidence 0.41 Published 2007 Journal J Circadian Rhythms Section Abstract Doc Link PMC1803776 Disease Relevance 0.65 Pain Relevance 0.05
Furthermore, we demonstrate that pharmacological inhibition of GSK3 activity by kenpaullone, a known antagonist of GSK3 activity, as well as by lithium, a direct inhibitor of GSK3 and the most common treatment for BPD, induces a phase delay in mPer2 transcription that resembles the effect observed with GSK3 knockdown.


Negative_regulation (inhibition) of GSK3 associated with antagonist and bronchopulmonary dysplasia
18) Confidence 0.41 Published 2007 Journal J Circadian Rhythms Section Abstract Doc Link PMC1803776 Disease Relevance 0.52 Pain Relevance 0.08
Nevertheless, (i) the cyclical and episodic nature of BPD symptoms, (ii) the prevalence of circadian rhythm abnormalities in BPD, (iii) the consistent evolutionarily conserved period/phase altering effects of lithium, (iv) the direct inhibition of GSK3 by lithium in vivo and in vitro, and (v) the role of Sgg/GSK3 in the modulation of period length in fruit fly and murine clocks, places GSK3 at the forefront of the short list of known physiological targets in the therapeutic efficacy of lithium in BPD.


Negative_regulation (inhibition) of GSK3 associated with congenital anomalies and bronchopulmonary dysplasia
19) Confidence 0.41 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0.91 Pain Relevance 0.30
We demonstrate that genetic depletion of GSK3 in synchronized oscillating MEFs results in a significant delay in the periodicity of the endogenous clock mechanism, particularly in the cycling period of mPer2.
Negative_regulation (depletion) of GSK3 in MEFs
20) Confidence 0.41 Published 2007 Journal J Circadian Rhythms Section Abstract Doc Link PMC1803776 Disease Relevance 0.55 Pain Relevance 0.07

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