INT160853

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Context Info
Confidence 0.72
First Reported 2004
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 87
Total Number 93
Disease Relevance 20.06
Pain Relevance 5.31

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

transport (Syp) protein complex (Syp)
Anatomy Link Frequency
brain 7
neurons 5
olfactory bulbs 3
molecular layer 2
cerebellum 2
Syp (Mus musculus)
Syp - S129A (2)
Pain Link Frequency Relevance Heat
Substantia nigra 814 100.00 Very High Very High Very High
Dopamine 1262 99.82 Very High Very High Very High
dopaminergic neurodegeneration 35 96.08 Very High Very High Very High
Neuritis 3 95.88 Very High Very High Very High
Catecholamine 366 94.72 High High
imagery 74 92.56 High High
Inflammation 124 85.76 High High
midbrain 280 85.56 High High
long-term potentiation 45 81.92 Quite High
Pain 65 80.16 Quite High
Disease Link Frequency Relevance Heat
Targeted Disruption 1162 100.00 Very High Very High Very High
Adhesions 27 100.00 Very High Very High Very High
Parkinson's Disease 1185 99.84 Very High Very High Very High
Disease 427 99.84 Very High Very High Very High
Aging 186 99.84 Very High Very High Very High
Stroke 145 99.78 Very High Very High Very High
Apoptosis 210 99.24 Very High Very High Very High
Neurodegenerative Disease 121 98.96 Very High Very High Very High
Middle Cerebral Artery Infarction 52 98.84 Very High Very High Very High
Stress 136 98.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
As an additional control, we also evaluated phosphorylation of the extracellular signal-regulated kinase (ERK) in a-Syn MN9D cells, because ERK is a PP2A substrate (53, 54) that also regulates TH (55, 56) and because others have shown that ERK activity is inhibited by a-Syn overexpression (57).
Gene_expression (overexpression) of Syn
1) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.03
These findings raised the possibility that phosphorylation of other TH serines might be similarly affected by a-Syn overexpression.
Gene_expression (overexpression) of Syn
2) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.47 Pain Relevance 0
Our findings in ASKO mice demonstrated that a loss of a-Syn produced the opposite effect on TH and PP2A imply that enzymatic dysregulation can also occur by a loss of soluble a-Syn, as those mice express normal levels of ?
Gene_expression (produced) of Syn
3) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.11 Pain Relevance 0.06
a-Syn overexpression in WT-Syn++ and A53T-Syn++ mice reduced TH-Ser-19 phosphorylation in vivo, suggesting that, as in dopaminergic cell lines, both forms of a-Syn regulate TH similarly in the brain.
Gene_expression (overexpression) of Syn in brain
4) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.38 Pain Relevance 0.16
We noted similar effects of transiently overexpressed a-Syn on TH-Ser(P)-19 in MN9D cells as well as in PC12 cells in which a-Syn overexpression is inducible (not shown), confirming an association between a-Syn and TH that reduces TH-Ser(P)-19 levels.
Gene_expression (overexpression) of Syn
5) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
The second goal of the study was to determine the in vivo relevance of a-Syn-mediated TH modulation using a-Syn-overexpressing and null transgenic mice.
Gene_expression (overexpressing) of Syn associated with targeted disruption
6) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.23 Pain Relevance 0.05
We noted similar effects of transiently overexpressed a-Syn on TH-Ser(P)-19 in MN9D cells as well as in PC12 cells in which a-Syn overexpression is inducible (not shown), confirming an association between a-Syn and TH that reduces TH-Ser(P)-19 levels.
Gene_expression (overexpressed) of Syn
7) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
Because we previously established that a-Syn overexpression reduces TH-Ser(P)-40 in MN9D cells (43) and reconfirmed this same effect here for wild type a-Syn-overexpressing mice, the data for the remainder of the manuscript will focus entirely on our novel findings related to TH-Ser(P)-19.


Gene_expression (overexpression) of Syn
8) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.06
In vivo evidence, showing that a-Syn reduced Ser(P)-19 on TH, was obtained in transgenic mice expressing human a-Syn under the control of the TH-promoter (Syn++).
Gene_expression (expressing) of Syn associated with targeted disruption
9) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.30 Pain Relevance 0.12
Yet despite a-Syn being overexpressed only in this small group of cells, we could measure a significant increase in PP2A activity in WT-Syn++ mice compared with Non-Tg control olfactory bulbs (Fig. 3F, left side; p < 0.01, Student's t test).
Gene_expression (overexpressed) of Syn in olfactory bulbs
10) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 Pain Relevance 0
Together these findings strongly suggest that overexpression of a-Syn in TH-promoter mouse dopaminergic tissues reduced TH phosphorylation at TH-Ser(P)-19 and TH-Ser(P)-40, resulting in lower TH activity.
Gene_expression (overexpression) of Syn
11) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
g/ml G418 (Invitrogen) and used at low passage to sustain a-Syn expression as confirmed using immunoblots (9, 43, 44).
Gene_expression (expression) of Syn
12) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.25 Pain Relevance 0
These findings are supported by our in vivo studies (Figs. 3 and 6), suggesting the possibility that (i) TH inhibition may be caused by an up-regulation of PP2A activity that is triggered by a-Syn overexpression, (ii) PP2A activation and TH inhibition may be independently triggered by a-Syn overexpression leading to interactions that affect both enzymes, or (iii) that TH inhibition may be an additive consequence of a-Syn overexpression and its ability to activate PP2A.
Gene_expression (overexpression) of Syn
13) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.11 Pain Relevance 0.06
Based on the above findings, we surmised that if a-Syn inhibits TH and stimulates PP2A in dopaminergic neurons in vivo, then the absence of a-Syn in ASKO mice would produce effects opposite those of a-Syn overexpression.
Gene_expression (overexpression) of Syn in dopaminergic neurons
14) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.04
Overexpression of WT or Dephosphorylation Mutant a-Syn, S129A, Stimulates PP2A Activity and Reduces TH Phosphorylation in MN9D Cells, with a Bigger Effect of S129A
Gene_expression (Overexpression) of Syn
15) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.09 Pain Relevance 0.03
Total TH levels remain similar; however, on occasion we noted less total TH in a-Syn-overexpressing MN9D cells.
Gene_expression (overexpressing) of Syn
16) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
These findings are supported by our in vivo studies (Figs. 3 and 6), suggesting the possibility that (i) TH inhibition may be caused by an up-regulation of PP2A activity that is triggered by a-Syn overexpression, (ii) PP2A activation and TH inhibition may be independently triggered by a-Syn overexpression leading to interactions that affect both enzymes, or (iii) that TH inhibition may be an additive consequence of a-Syn overexpression and its ability to activate PP2A.
Gene_expression (overexpression) of Syn
17) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.06 Pain Relevance 0.04
When we assessed if higher levels of a-Syn expression correlated strongly with lower TH phosphorylation in individual WT-Syn++ mice, we found a significant negative correlation.
Gene_expression (expression) of Syn
18) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.18 Pain Relevance 0
These findings are supported by our in vivo studies (Figs. 3 and 6), suggesting the possibility that (i) TH inhibition may be caused by an up-regulation of PP2A activity that is triggered by a-Syn overexpression, (ii) PP2A activation and TH inhibition may be independently triggered by a-Syn overexpression leading to interactions that affect both enzymes, or (iii) that TH inhibition may be an additive consequence of a-Syn overexpression and its ability to activate PP2A.
Gene_expression (overexpression) of Syn
19) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 Pain Relevance 0.04
In contrast, rats that overexpress WT or S129A a-Syn delivered by adeno-associated virus (AAV) develop pathology by 8 weeks, although rats transduced with S129D AAV do not (68, 70).
Gene_expression (overexpress) of Syn
20) Confidence 0.72 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.28 Pain Relevance 0.06

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