INT156373

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Context Info
Confidence 0.39
First Reported 2008
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 4
Total Number 15
Disease Relevance 1.54
Pain Relevance 2.30

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

transport (Sv2a) transmembrane transporter activity (Sv2a) endoplasmic reticulum (Sv2a)
transmembrane transport (Sv2a) cytoplasm (Sv2a)
Anatomy Link Frequency
neurons 6
spinal cord 1
synaptic cleft 1
cornea 1
SV2A 1
Sv2a (Mus musculus)
Pain Link Frequency Relevance Heat
Neurotransmitter 71 100.00 Very High Very High Very High
Spinal cord 554 99.08 Very High Very High Very High
Glutamate 38 93.40 High High
Potency 4 90.64 High High
Gabapentin 40 80.80 Quite High
gABA 36 79.96 Quite High
pregabalin 28 78.04 Quite High
Eae 3 74.88 Quite High
GABAergic 16 73.04 Quite High
antiepileptic Drug 94 72.40 Quite High
Disease Link Frequency Relevance Heat
Epilepsy 48 97.44 Very High Very High Very High
Absence Epilepsy 6 95.64 Very High Very High Very High
Convulsion 18 89.72 High High
Lifespan 1 85.60 High High
Infection 48 83.52 Quite High
Anaerobic Bacterial Infections 264 80.00 Quite High
Targeted Disruption 72 78.64 Quite High
Toxicity 18 75.56 Quite High
Anxiety Disorder 14 75.00 Quite High
Pain 4 71.04 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Furthermore, SV2 is critical for the binding and entry of TeNT into neurons.
SV2 Binding (binding) of in neurons
1) Confidence 0.39 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.08 Pain Relevance 0.08
As opposed to the previous model, the peripheral receptor, rather than SV2, has a higher affinity for TeNT.
SV2 Binding (affinity) of
2) Confidence 0.39 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0 Pain Relevance 0
Synaptic vesicle protein 2A (SV2A) is involved in neurotransmitter release and has been identified as the binding site for levetiracetam (Keppra), a novel antiepileptic drug.
SV2A Binding (binding) of in SV2A associated with neurotransmitter
3) Confidence 0.36 Published 2009 Journal Behav. Brain Res. Section Abstract Doc Link 19041904 Disease Relevance 0.23 Pain Relevance 0.18
To further confirm that TeNT associated with SV2, we used HCR/T to see if it could compete with BoNT/E for binding to its native receptor, SV2, on hippocampal neurons.
SV2 Binding (associated) of in neurons
4) Confidence 0.34 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.07 Pain Relevance 0
Consistent with previous reports, we detected that BoNT/B associated with syt I and BoNT/E with SV2, but surprisingly, we observed that TeNT also strongly associated with SV2 (Figure 4A).
SV2 Binding (associated) of
5) Confidence 0.34 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.08 Pain Relevance 0.03
In addition, the higher affinity of SV2 for TeNT would allow for efficient capture of the toxin once it has dissociated from the MN, thus favoring binding and entry into the upstream inhibitory neuron.
SV2 Binding (affinity) of in neuron
6) Confidence 0.34 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.05 Pain Relevance 0.03
These results further demonstrate that SV2 plays a critical role in the binding of TeNT to inhibitory terminals in the spinal cord.
SV2 Binding (binding) of in spinal cord associated with spinal cord
7) Confidence 0.33 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.15 Pain Relevance 0.17
Notably, we found that an excess amount of TeNT efficiently occluded the binding and entry of BoNT/E, consistent with competitive binding for sites on SV2.
SV2 Binding (binding) of
8) Confidence 0.33 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0 Pain Relevance 0.18
Thus, both SV2A and B are important for TeNT to recognize and associate with the surface of central neurons.
SV2A Binding (associate) of in neurons
9) Confidence 0.30 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.08 Pain Relevance 0.07
Thus, both SV2A and B are important for TeNT to recognize and associate with the surface of central neurons.
SV2A Binding (recognize) of in neurons
10) Confidence 0.30 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.08 Pain Relevance 0.07
Consistent with previous reports, we detected that BoNT/B associated with syt I and BoNT/E with SV2, but surprisingly, we observed that TeNT also strongly associated with SV2 (Figure 4A).
SV2 Binding (associated) of
11) Confidence 0.30 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.07 Pain Relevance 0
These modifications result in a potentiated binding to the SV2A protein, up to 10-fold compared to levetiracetam in several models for epilepsy, like cornea kindling and the GAERS absence seizure model (Crowder et al. 1999, Lynch et al. 2004, Bennett et al. 2007, Von Rosenstiel et al. 2007).


SV2A protein Binding (binding) of in cornea associated with epilepsy and absence epilepsy
12) Confidence 0.29 Published 2008 Journal Perspectives in Medicinal Chemistry Section Body Doc Link PMC2746576 Disease Relevance 0.19 Pain Relevance 0.52
To further confirm that TeNT associated with SV2, we used HCR/T to see if it could compete with BoNT/E for binding to its native receptor, SV2, on hippocampal neurons.
SV2 Binding (binding) of in neurons
13) Confidence 0.29 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.07 Pain Relevance 0
However, it seems likely that these two toxins compete for binding (Figure 4B–C) due to a steric hindrance; two different toxin molecules are unlikely to be able to simultaneously bind to the relatively small intra-lumenal loops of SV2 that are exposed to the extracellular milieu during exocytosis.
SV2 Binding (bind) of
14) Confidence 0.29 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.07 Pain Relevance 0
It is still unclear how levetiracetam and SV2A interact, but it has been proposed that it is essential for exocytosis of neurotransmitter from the presynaptic neuron into the synaptic cleft and may prevent exocytosis of glutamate, since there is a correlation between binding affinity and potency in suppressing tonic seizures in audiogenic sensitive mice (Lynch et al. 2004).
SV2A Binding (interact) of in synaptic cleft associated with glutamate, neurotransmitter, convulsion and potency
15) Confidence 0.21 Published 2008 Journal Perspectives in Medicinal Chemistry Section Body Doc Link PMC2746576 Disease Relevance 0.32 Pain Relevance 0.98

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