INT245670

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Context Info
Confidence 0.65
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 37
Total Number 37
Disease Relevance 7.34
Pain Relevance 1.25

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 4
white matter 4
molecular layer 2
PP2A 2
olfactory bulbs 2
Syp (Mus musculus)
Syp - S129A (1)
Pain Link Frequency Relevance Heat
Dopamine 626 99.82 Very High Very High Very High
Catecholamine 186 94.72 High High
Substantia nigra 316 93.80 High High
GABAergic 1 66.68 Quite High
Hippocampus 20 56.56 Quite High
Thalamus 10 55.52 Quite High
ischemia 23 50.00 Quite Low
dopaminergic neurodegeneration 5 50.00 Quite Low
Abeta 1 50.00 Quite Low
Neuritis 1 45.96 Quite Low
Disease Link Frequency Relevance Heat
Parkinson's Disease 570 99.84 Very High Very High Very High
Targeted Disruption 331 99.60 Very High Very High Very High
Apoptosis 110 99.24 Very High Very High Very High
Middle Cerebral Artery Infarction 52 98.84 Very High Very High Very High
Disease 74 98.64 Very High Very High Very High
Stroke 145 96.52 Very High Very High Very High
Movement Disorders 31 95.60 Very High Very High Very High
Aging 93 93.92 High High
Neurodegenerative Disease 44 86.56 High High
Stress 64 84.80 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
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.
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of Syn
1) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
To measure the impact of Ser(P)-129 a-Syn on PP2A and TH, we transiently overexpressed WT-Syn or S129A-Syn mutant a-Syn, with alanine substituted for serine at amino acid 129.
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of Syn
2) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 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.
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn
3) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.11 Pain Relevance 0.06
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).
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn
4) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.03
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).
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of Syn in olfactory bulbs
5) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 Pain Relevance 0
These findings raised the possibility that phosphorylation of other TH serines might be similarly affected by a-Syn overexpression.
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn
6) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.47 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.
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn
7) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.06 Pain Relevance 0.04
As noted for WT-Syn++ TH-promoter mice, the effect of a-Syn on PP2A in A53T-Syn++ olfactory bulb appeared to be diluted by a-Syn being overexpressed in such a small pool of neurons in that brain region.
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of Syn in brain
8) Confidence 0.65 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.03
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.
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn
9) Confidence 0.65 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.
Positive_regulation (overexpressing) of Gene_expression (overexpressing) of Syn associated with targeted disruption
10) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.23 Pain Relevance 0.05
In MN9D cells, a-Syn overexpression reduced TH serine 19 phosphorylation (Ser(P)-19).
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn
11) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878529 Disease Relevance 0.15 Pain Relevance 0.13
In cells, a-Syn overexpression activates PP2A.
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn in PP2A
12) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878529 Disease Relevance 0.14 Pain Relevance 0.13
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
Positive_regulation (Overexpression) of Gene_expression (Overexpression) of Syn
13) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.09 Pain Relevance 0.03
To evaluate if in vivo overexpression of a-Syn altered TH phosphorylation, we compared striatal immunoblots from homozygous WT a-Syn-overexpressing TH-promoter mice (WT-Syn++) to non-transgenic control mice (Non-Tg) in the same genetic background in which total a-Syn overexpression is ?
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn associated with targeted disruption
14) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.28 Pain Relevance 0.04
We next explored the impact of PP2A inhibition in WT a-Syn-overexpressing MN9D cells and saw a pronounced increase in TH-Ser(P)-19 levels.
Positive_regulation (overexpressing) of Gene_expression (overexpressing) of Syn
15) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0
To measure the impact of Ser(P)-129 a-Syn on PP2A and TH, we transiently overexpressed WT-Syn or S129A-Syn mutant a-Syn, with alanine substituted for serine at amino acid 129.
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of Syn
16) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.07 Pain Relevance 0
In our cells transfected with GFP, WT-Syn, or S129A-Syn for 48–72 h we saw equivalent transfection efficiency and cellular morphology (not shown).
Positive_regulation (transfected) of Gene_expression (transfected) of Syn
17) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.06 Pain Relevance 0
80% loss of nigrostriatal dopamine (47). a-Syn overexpression is ?
Positive_regulation (overexpression) of Gene_expression (overexpression) of Syn associated with dopamine
18) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.46 Pain Relevance 0.08
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).
Positive_regulation (overexpress) of Gene_expression (overexpress) of Syn
19) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.28 Pain Relevance 0.06
Evidence for regulation of TH by a-Syn in vivo was further corroborated by our data in mice lacking a-Syn, in which we saw effects opposite to those observed in a-Syn-overexpressing mice; namely, the ASKO mice had higher TH-Ser(P)-19 levels and significantly more active TH.
Positive_regulation (overexpressing) of Gene_expression (overexpressing) of Syn
20) Confidence 0.47 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0.30 Pain Relevance 0.16

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