INT116762

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Context Info
Confidence 0.70
First Reported 2004
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 10
Total Number 16
Disease Relevance 9.79
Pain Relevance 0.19

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

signal transduction (IKBKAP) nucleolus (IKBKAP) nucleus (IKBKAP)
protein complex assembly (IKBKAP) DNA binding (IKBKAP) cytoplasm (IKBKAP)
Anatomy Link Frequency
neuronal 2
leukocytes 2
neural crest 2
fibroblasts 2
IKBKAP (Homo sapiens)
Pain Link Frequency Relevance Heat
Potency 15 98.50 Very High Very High Very High
unmyelinated 1 84.56 Quite High
Pain 16 72.40 Quite High
imagery 16 5.00 Very Low Very Low Very Low
Peripheral nervous system 8 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Familial Dysautonomia 1497 100.00 Very High Very High Very High
Toxicity 35 96.36 Very High Very High Very High
Targeted Disruption 24 91.24 High High
Spinal Muscular Atrophy 7 88.92 High High
Rare Diseases 16 87.96 High High
Neuromuscular Disease 7 87.96 High High
Cognitive Disorder 49 87.92 High High
Congenital Anomalies 14 86.52 High High
Disease 102 85.00 Quite High
Neuropathic Pain 22 84.96 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Increasing the expression level of IKAP mRNA over a certain threshold leads to an increase in full-length IKAP protein levels.
Positive_regulation (Increasing) of Gene_expression (expression) of IKAP mRNA
1) Confidence 0.70 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.64 Pain Relevance 0
For FD, several drugs, including kinetin and tocotrienol, increase the levels of wild-type IKAP mRNA and protein.
Positive_regulation (increase) of Gene_expression (levels) of IKAP mRNA associated with familial dysautonomia
2) Confidence 0.70 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.52 Pain Relevance 0
Moreover, kinetin, by improving IKBKAP exon 20 recognition, restores IKBKAP transcript levels in FD hOE-MSCs similar to those observed in control cells (Figure 7G).
Positive_regulation (restores) of Gene_expression (levels) of IKBKAP associated with familial dysautonomia
3) Confidence 0.69 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.24 Pain Relevance 0
In previous studies, one compound, kinetin (6-furfurylaminopurine) was found to correct IKBKAP splicing and increase IKAP/hELP1 production in FD cells [35].
Positive_regulation (increase) of Gene_expression (production) of IKAP/hELP1 associated with familial dysautonomia
4) Confidence 0.69 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.57 Pain Relevance 0
Mutations result in tissue-specific expression of mutant IkappaB kinase-associated protein (IKAP).
Positive_regulation (result) of Gene_expression (expression) of IKAP
5) Confidence 0.67 Published 2004 Journal Muscle Nerve Section Abstract Doc Link 14981733 Disease Relevance 0.62 Pain Relevance 0.11
However, the serine-based substance, phosphatidylserine (produced by Enzymotec under the Sharp•PS® brand), significantly increased IKAP mRNA and IKAP protein levels in cells derived from FD patients.
Positive_regulation (increased) of Gene_expression (levels) of IKAP protein associated with familial dysautonomia
6) Confidence 0.50 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.64 Pain Relevance 0
In contrast, tocotrienol, a member of the vitamin E family that was reported to induce IKAP expression in FD cells [36], [37], [38], did not affect IKAP mRNA expression in our system (Figure 7B); this observation is similar to that of another publication [39].
Positive_regulation (induce) of Gene_expression (expression) of IKAP associated with familial dysautonomia
7) Confidence 0.50 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.77 Pain Relevance 0
Here we show that phosphatidylserine (PS), an FDA-approved food supplement, increased IKAP mRNA levels in cells derived from FD patients.
Positive_regulation (increased) of Gene_expression (levels) of IKAP mRNA associated with familial dysautonomia
8) Confidence 0.50 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3012102 Disease Relevance 0.72 Pain Relevance 0
However, the serine-based substance, phosphatidylserine (produced by Enzymotec under the Sharp•PS® brand), significantly increased IKAP mRNA and IKAP protein levels in cells derived from FD patients.
Positive_regulation (increased) of Gene_expression (levels) of IKAP mRNA associated with familial dysautonomia
9) Confidence 0.50 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.64 Pain Relevance 0
The mutation results in a tissue-specific splicing defect: Exon 20 is skipped, leading to reduced IKAP protein expression.
Positive_regulation (leading) of Gene_expression (expression) of IKAP protein
10) Confidence 0.50 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3012102 Disease Relevance 0.72 Pain Relevance 0
Consistent results were observed for IKAP/hELP1 protein expression by western blot analysis, although a strong decrease of protein amount appeared after 24 h of wash out (Figure 7F).
Positive_regulation (observed) of Gene_expression (expression) of IKAP/hELP1
11) Confidence 0.50 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.20 Pain Relevance 0
Additionally, hOE-MSCs are an appropriate model for validating the potency of therapeutic agents such as kinetin, a cytokinin that has been shown to increase IKBKAP mRNA and protein expression in FD cell lines and in vivo models [20], [22], [35], [36] as well as in leukocytes of healthy carriers of the FD mutation [37].


Positive_regulation (increase) of Gene_expression (expression) of IKBKAP in leukocytes associated with familial dysautonomia and potency
12) Confidence 0.50 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.90 Pain Relevance 0.05
Time-course experiments of kinetin treatment revealed that the drug acts quite rapidly on correcting IKBKAP mRNA splicing and enhancing IKAP/hELP1 synthesis, but its effects last only a short time after removal (Figure 7E and F).
Positive_regulation (enhancing) of Gene_expression (synthesis) of IKAP/hELP1
13) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.44 Pain Relevance 0
However, a recent study suggests that IKAP/hELP1 expression is much higher in neurons compared to fibroblasts [21], and fibroblasts do not exhibit the same ratio of IKBKAP exon 20 including?
Positive_regulation (higher) of Gene_expression (expression) of IKAP/hELP1 in fibroblasts
14) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.96 Pain Relevance 0
When subjected to immunostaining, all hOE-MSCs derived from control and FD biopsies express the neural stem cell–specific marker nestin (Figure 1D and 1E) and the immature neuronal marker ?
Positive_regulation (derived) of Gene_expression (biopsies) of FD in neuronal associated with familial dysautonomia
15) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.76 Pain Relevance 0.03
Interestingly, Lee and colleagues determined that the neuron-specific splicing factor NOVA1 [61] was underexpressed in FD versus control iPS cell-derived neural crest precursors [22].
Positive_regulation (underexpressed) of Gene_expression (underexpressed) of FD in neural crest associated with familial dysautonomia
16) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.45 Pain Relevance 0

General Comments

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