INT87314

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Context Info
Confidence 0.78
First Reported 2000
Last Reported 2010
Negated 3
Speculated 0
Reported most in Body
Documents 112
Total Number 112
Disease Relevance 55.82
Pain Relevance 3.03

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

Golgi apparatus (Htt) endoplasmic reticulum (Htt) mitochondrion organization (Htt)
embryo development (Htt) protein complex (Htt) cytoplasm (Htt)
Anatomy Link Frequency
neurons 10
brain 5
striatum 3
HeLa 3
muscle 3
Htt (Mus musculus)
Pain Link Frequency Relevance Heat
adenocard 11 99.16 Very High Very High Very High
gABA 21 97.72 Very High Very High Very High
Central nervous system 106 96.64 Very High Very High Very High
substance P 10 96.58 Very High Very High Very High
Enkephalin 41 96.32 Very High Very High Very High
Pyramidal cell 74 96.00 Very High Very High Very High
medulla 108 95.76 Very High Very High Very High
Hippocampus 84 94.84 High High
cerebral cortex 242 94.32 High High
Neurotransmitter 36 93.70 High High
Disease Link Frequency Relevance Heat
Disease 4650 100.00 Very High Very High Very High
Targeted Disruption 1997 100.00 Very High Very High Very High
Neurodegenerative Disease 564 100.00 Very High Very High Very High
Obesity 151 100.00 Very High Very High Very High
Huntington's Chorea 43 100.00 Very High Very High Very High
Toxicity 780 99.80 Very High Very High Very High
Frailty 329 99.64 Very High Very High Very High
Muscular Atrophy 72 98.74 Very High Very High Very High
Lifespan 317 98.72 Very High Very High Very High
Neuropathic Pain 48 98.64 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder caused by a CAG repeat expansion in the ubiquitously expressed HD gene resulting in an abnormally long polyglutamine repeat in the huntingtin protein.
Gene_expression (expressed) of HD gene associated with neurodegenerative disease and disease
1) Confidence 0.78 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2778556 Disease Relevance 0.85 Pain Relevance 0
Additional factors that might influence the propensity to form inclusions in a particular cell type could include expression level of the R6/2 transcript or Hdh gene, Htt proteolysis and protein folding and clearance networks.
Gene_expression (expression) of Hdh
2) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.82 Pain Relevance 0.06
Therefore, we have demonstrated that the peripheral pathology documented in the R6/2 mice is not the result of the aberrant expression of a small N-terminal fragment of mutant Htt as it is also present in a genetically precise HD mouse model in which an expanded CAG repeat has been inserted into the mouse Hdh gene.
Gene_expression (expression) of Htt associated with disease
3) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.52 Pain Relevance 0
Although HD is a neurodegenerative disorder, the HD gene is ubiquitously expressed, and whilst it is understandable that HD research is predominantly focussed on the central nervous system (CNS), evidence is accumulating to suggest that some HD symptoms may be caused by a peripheral pathology.
Gene_expression (expressed) of HD gene in central nervous system associated with central nervous system, neurodegenerative disease and disease
4) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.86 Pain Relevance 0.10
This hypothesis was derived from the observation that two critical mediators of the genotoxic stress signal pathway, p53 and p73, are activated in cultured cells and mouse models expressing mutant huntingtin (Htt) protein (Steffan et al., 2000; Bae et al., 2005; Hoshino et al., 2006).
Gene_expression (expressing) of huntingtin associated with dna damage
5) Confidence 0.72 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.71 Pain Relevance 0
Expression of Htt and DsRed was induced by 1 µg/ml doxycycline.


Gene_expression (Expression) of Htt
6) Confidence 0.72 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.09 Pain Relevance 0.04
We found that an amount of mutant Htt almost equivalent to the endogenous Htt expression level was sufficient for inhibition of DNA–PK activity (Fig. 5 F).
Gene_expression (expression) of Htt
7) Confidence 0.72 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.07 Pain Relevance 0
This hypothesis was derived from the observation that two critical mediators of the genotoxic stress signal pathway, p53 and p73, are activated in cultured cells and mouse models expressing mutant huntingtin (Htt) protein (Steffan et al., 2000; Bae et al., 2005; Hoshino et al., 2006).
Gene_expression (expressing) of Htt associated with dna damage
8) Confidence 0.72 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.71 Pain Relevance 0
Our findings indicate that neither HD pathogenesis, nor DNA repair gene expression levels is a major determinant of the tissue specificity of somatic instability.
Gene_expression (expression) of HD associated with disease
9) Confidence 0.68 Published 2010 Journal BMC Syst Biol Section Body Doc Link PMC2856555 Disease Relevance 0.10 Pain Relevance 0
To determine whether neurons lacking huntingtin can participate in development and survive in postnatal brain, we used two approaches in an effort to create mice consisting of wild-type cells and cells without huntingtin.
Neg (lacking) Gene_expression (lacking) of huntingtin in brain
10) Confidence 0.68 Published 2001 Journal J. Neurosci. Section Abstract Doc Link 11567051 Disease Relevance 0 Pain Relevance 0
Neurons lacking huntingtin differentially colonize brain and survive in chimeric mice.
Neg (lacking) Gene_expression (lacking) of huntingtin in brain
11) Confidence 0.68 Published 2001 Journal J. Neurosci. Section Title Doc Link 11567051 Disease Relevance 0.06 Pain Relevance 0.07
We had attributed these widespread pathologies in the R6/2 mouse brain to the expression of a small N-terminal fragment of Htt and therefore were surprised to find that it was also a feature of the HdhQ150/Q150 mice.
Gene_expression (expression) of Htt in brain
12) Confidence 0.68 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.72 Pain Relevance 0
The fibre diameters for each genotype were pooled HdhQ150/Q150, n?
Gene_expression (/) of HdhQ150
13) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.23 Pain Relevance 0
Symptomatic HD patients exhibit pronounced weight loss and muscle atrophy [17], [27], phenotypes that are modelled in both the R6/2 and HdhQ150 mouse models of HD [10], [13], [28], [29].
Gene_expression (models) of HdhQ150 in muscle associated with weight loss, muscular atrophy and disease
14) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.99 Pain Relevance 0
The fibre diameters for each genotype were pooled HdhQ150/Q150, n?
Gene_expression (pooled) of HdhQ150
15) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.23 Pain Relevance 0
Microarray expression profiles from both striatum [14] and cerebellum (Luthi-Carter and Bates, unpublished data) of the R6/2 and HdhQ150/Q150 mice were highly correlated.
Gene_expression (expression) of HdhQ150 in cerebellum
16) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2778556 Disease Relevance 0.89 Pain Relevance 0
Western blot analysis with primary cortical neurons expressing mutant Htt showed that protein levels of Ku70 and Ku80 but not of DNA–PKcs transiently increased at day 1, decreased from day 1 to day 6 after infection, and returned to the initial level (Fig. 6, A–C).
Gene_expression (expressing) of mutant Htt in neurons associated with infection
17) Confidence 0.63 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.09 Pain Relevance 0
These results (Fig. 3 D and Fig. 5 F) support that mutant Htt expressed in human patients could impair Ku70-mediated DNA damage repair.
Gene_expression (expressed) of mutant Htt
18) Confidence 0.63 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.06 Pain Relevance 0
Meanwhile, mutant Htt expression did not suppress activities of other kinases such as Cdk1/Cdc2 or MAPK/extracellular-regulated kinase (ERK; Fig. 5 F), supporting the view that the effect of mutant Htt on DNA–PK could be specific to some extent.
Gene_expression (expression) of mutant Htt
19) Confidence 0.63 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.06 Pain Relevance 0
Therefore, we tested how Ku70, Ku80, and DNA–PKcs respond to mutant Htt expression.
Gene_expression (expression) of mutant Htt
20) Confidence 0.63 Published 2010 Journal The Journal of Cell Biology Section Body Doc Link PMC2867301 Disease Relevance 0.08 Pain Relevance 0

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