INT106559

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Context Info
Confidence 0.43
First Reported 2002
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 23
Total Number 24
Disease Relevance 11.09
Pain Relevance 7.33

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 (Ntrk2) cytosol (Ntrk2) extracellular region (Bdnf)
plasma membrane (Ntrk2) cytoplasmic membrane-bounded vesicle (Bdnf) kinase activity (Ntrk2)
Anatomy Link Frequency
Brain 3
hippocampus 2
synapse 2
tail 1
spinal cord 1
Bdnf (Mus musculus)
Ntrk2 (Mus musculus)
Bdnf - V66M (1)
Pain Link Frequency Relevance Heat
neurotrophin 3 3 100.00 Very High Very High Very High
Lasting pain 13 99.96 Very High Very High Very High
Nerve growth factor 58 99.94 Very High Very High Very High
antidepressant 310 99.66 Very High Very High Very High
spinal dorsal horn 32 99.12 Very High Very High Very High
GABAergic 8 98.98 Very High Very High Very High
Kinase C 28 98.72 Very High Very High Very High
tRK receptor 1 98.40 Very High Very High Very High
Spinal cord 7 98.12 Very High Very High Very High
Inflammation 102 98.08 Very High Very High Very High
Disease Link Frequency Relevance Heat
Nociception 82 100.00 Very High Very High Very High
Pain 76 99.96 Very High Very High Very High
INFLAMMATION 113 98.08 Very High Very High Very High
Neurological Disease 20 97.88 Very High Very High Very High
Depression 358 97.52 Very High Very High Very High
Apoptosis 109 97.02 Very High Very High Very High
Neuropathic Pain 50 96.88 Very High Very High Very High
Hyperalgesia 37 96.76 Very High Very High Very High
Targeted Disruption 278 95.92 Very High Very High Very High
Stroke 22 95.76 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
These findings suggest the possibility that the binding of BDNF to full-length TrkB and subsequent its activation may play a critical role in the development of neuropathic pain-like thermal hyperalgesia induced by nerve injury in mice.
BDNF Spec (like) Binding (binding) of TrkB in nerve associated with nervous system injury, thermal hyperalgesia and neuropathic pain
1) Confidence 0.43 Published 2002 Journal Brain Res. Section Abstract Doc Link 12470870 Disease Relevance 0.74 Pain Relevance 0.73
Expression of the tyrosine kinase receptor that selectively binds BDNF, trkB, is increased in the spinal dorsal horn during inflammation as well.
BDNF Binding (binds) of trkB in spinal associated with inflammation and spinal dorsal horn
2) Confidence 0.41 Published 2002 Journal Pain Section Abstract Doc Link 12435470 Disease Relevance 1.07 Pain Relevance 0.72
Taken together, these findings suggest that the binding of spinally released BDNF to TrkB by nerve ligation may activate PKC within the spinal cord, resulting in the development of a neuropathic pain-like state in mice.
BDNF Binding (binding) of TrkB in spinal cord associated with kinase c, neuropathic pain and spinal cord
3) Confidence 0.41 Published 2005 Journal J. Neurochem. Section Abstract Doc Link 15836617 Disease Relevance 0.63 Pain Relevance 0.84
The interaction of neurotrophins with the Trk receptors is specific: NGF binds with TrkA, BDNF and NT 4 both bind with TrkB, and NT 3 binds with the highest affinity to TrkC but is also capable of signaling through TrkA and TrkB.
BDNF Binding (bind) of TrkB associated with nerve growth factor
4) Confidence 0.39 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.13 Pain Relevance 0.19
Using the TrkB inhibitor K-252a, or mice deficient for the common neurotrophin receptor p75(NTR), the regulation of GABAergic activity was shown specifically to be mediated by BDNF binding to the neurotrophin receptor TrkB.
BDNF Binding (binding) of TrkB associated with gabaergic
5) Confidence 0.37 Published 2009 Journal J. Neurosci. Section Abstract Doc Link 19812317 Disease Relevance 0 Pain Relevance 0.50
Recently, it has been shown that pro-BDNF binds preferentially to p75NTR and elicits apoptosis as opposed to mature BDNF, which binds weakly with p75NTR but with high affinity to TrkB, where it exerts neuroprotective activity.60,225 Thus, pro-BDNF and mature BDNF cause opposite physiological actions through binding to p75NTR and TrkB receptors, respectively.55 In fact, it has been shown that pro-BDNF facilitates long-term depression via activation of p75NTR.226 On the other hand, TrkB plays a critical role in early-phase long-term potentiation227 and conversion of pro-BDNF to mature BDNF is essential for TrkB-mediated late-phase long-term potentiation.61 In a recent preliminary study, we observed that the level of pro-BDNF is increased PFC and hippocampus of suicide subjects (unpublished observation), whereas a recent genetic study suggests that the S205L polymorphism, which substitutes a serine with a leucine residue, of the p75NTR gene is associated with attempted suicide.228 These studies reveal the crucial roles of pro-BDNF and p75NTR in suicidal behavior.


BDNF Binding (binding) of TrkB in hippocampus associated with suicidal behaviour, depression, hippocampus, long-term potentiation and apoptosis
6) Confidence 0.34 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.73 Pain Relevance 0.17
Recently, it has been shown that pro-BDNF binds preferentially to p75NTR and elicits apoptosis as opposed to mature BDNF, which binds weakly with p75NTR but with high affinity to TrkB, where it exerts neuroprotective activity.60,225 Thus, pro-BDNF and mature BDNF cause opposite physiological actions through binding to p75NTR and TrkB receptors, respectively.55 In fact, it has been shown that pro-BDNF facilitates long-term depression via activation of p75NTR.226 On the other hand, TrkB plays a critical role in early-phase long-term potentiation227 and conversion of pro-BDNF to mature BDNF is essential for TrkB-mediated late-phase long-term potentiation.61 In a recent preliminary study, we observed that the level of pro-BDNF is increased PFC and hippocampus of suicide subjects (unpublished observation), whereas a recent genetic study suggests that the S205L polymorphism, which substitutes a serine with a leucine residue, of the p75NTR gene is associated with attempted suicide.228 These studies reveal the crucial roles of pro-BDNF and p75NTR in suicidal behavior.


BDNF Binding (binding) of TrkB in hippocampus associated with suicidal behaviour, depression, hippocampus, long-term potentiation and apoptosis
7) Confidence 0.34 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2732010 Disease Relevance 0.73 Pain Relevance 0.17
BDNF exerts effects on nociception by binding to trkB.FL and initiating intracellular signaling cascades that lead to transcriptional changes.
BDNF Binding (binding) of trkB associated with nociception
8) Confidence 0.33 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.56 Pain Relevance 0.36
However, competition assay shows that deoxygedunin is unable to compete off BDNF bound to TrkB (data not shown).
BDNF Binding (bound) of TrkB
9) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0 Pain Relevance 0
BDNF and TrkB receptor are targets for therapeutic intervention in various neurological diseases including neuroexcitotoxicity, stroke, depression, anxiety, neurodegeneration etc.
BDNF Binding (receptor) of TrkB associated with neurological disease, depression, stroke and anxiety disorder
10) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.59 Pain Relevance 0.17
Neurotrophins exert their biological functions on neurons through two transmembrane receptors: the p75 neurotrophin receptor (p75NTR) and the Trk receptor tyrosine kinases (NGF binds to TrkA, BDNF and NT-4/5 bind to TrkB, and NT-3 preferentially binds to TrkC) [3], [4].
BDNF Binding (bind) of TrkB in neurons associated with nerve growth factor
11) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.08 Pain Relevance 0.14
Recently, we found that one p75NTR missense polymorphism (S250L) was associated with the antidepressant response,53 and TrkB genetic variants may interact with the BDNF Val66Met polymorphism to contribute to the risk of geriatric depression.54 We also found that SNPs in glycogen synthase kinase-3beta (GSK3B), an important component in BDNF signaling, were associated with the therapeutic effects of antidepressants.55 In another study, we showed that genetic variants in plasminogen activator inhibitor type 1 gene (SERPINE1), which may be involved in the cleavage of proBDNF to mature BDNF in the brain,56 are related to MDD susceptibility and also the acute therapeutic response to antidepressants.57
BDNF (V66M) Binding (interact) of TrkB in cleavage associated with antidepressant and depression
12) Confidence 0.31 Published 2010 Journal Psychiatry Investigation Section Body Doc Link PMC3022309 Disease Relevance 0.18 Pain Relevance 0.54
Spine growth and synapse formation is also regulated by neurotrophic factors, such as Brain-Derived Neurotrophic Factor (BDNF), and the respective receptors for these neurotrophic factors, such as NTRK2 and NTRK3 [42,43].
BDNF Binding (receptors) of NTRK2 in synapse
13) Confidence 0.29 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2896956 Disease Relevance 0.39 Pain Relevance 0.07
Spine growth and synapse formation is also regulated by neurotrophic factors, such as Brain-Derived Neurotrophic Factor (BDNF), and the respective receptors for these neurotrophic factors, such as NTRK2 and NTRK3 [42,43].
Brain-Derived Neurotrophic Factor Binding (receptors) of NTRK2 in synapse
14) Confidence 0.29 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2896956 Disease Relevance 0.39 Pain Relevance 0.09
BDNF binding to TrkB triggers its dimerization through conformational changes and autophosphorylation of tyrosine residues in its intracellular domain, resulting in activation of the three major signaling pathways involving mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and phospholipase C-?
BDNF Binding (binding) of TrkB
15) Confidence 0.27 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2903477 Disease Relevance 0.26 Pain Relevance 0.15
The available evidence regarding trkB.T1 signaling suggests that BDNF binding to trkB.T1 causes increased intracellular calcium release [28].
BDNF Binding (binding) of trkB
16) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.45 Pain Relevance 0.41
The extracellular domain of trkB.T1 is identical to the full-length isoform, which enables high-affinity BDNF binding [15,16].
BDNF Binding (binding) of trkB
17) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 0.64 Pain Relevance 0.28
Most studies have focused on trkB.FL as the receptor responsible for BDNF-mediated nociception, since antibodies specific for trkB.FL [12] and abrogation of trkB.FL activation using the trkBF616A transgenic mouse [14] attenuate thermal and mechanical hypersensitivity.
BDNF-mediated Binding (nociception) of trkB associated with targeted disruption, nociception and hypersensitivity
18) Confidence 0.25 Published 2009 Journal Mol Pain Section Body Doc Link PMC2777863 Disease Relevance 1.11 Pain Relevance 0.61
In animal models of chronic pain, BDNF exerts its effects on nociceptive processing by binding to the full-length receptor tropomyosin-related kinase B (trkB.FL) and transducing intracellular signaling to produce nocifensive behaviors.
BDNF Binding (binding) of trkB associated with nociception and lasting pain
19) Confidence 0.24 Published 2009 Journal Mol Pain Section Abstract Doc Link PMC2777863 Disease Relevance 0.59 Pain Relevance 0.24
Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, control neurodevelopment and synaptic plasticity.
BDNF Binding (receptor) of TrkB in Brain
20) Confidence 0.22 Published 2007 Journal Nutr Metab (Lond) Section Body Doc Link PMC2018708 Disease Relevance 0.35 Pain Relevance 0.07

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