INT160994

Context Info Confidence 0.20 First Reported 2007 Last Reported 2011 Negated 0 Speculated 0 Reported most in Body Documents 9 Total Number 10 Disease Relevance 4.83 Pain Relevance 3.71

unfolded protein binding (St13) protein folding (St13) cytosol (St13) protein complex (St13) cytoplasm (St13)

Anatomy Link Frequency DA neurons 2 neurons 1 striatum 1 CPu 1 St13 (Mus musculus)

Pain Link Frequency Relevance Heat Dopamine 210 100.00 Antinociceptive 5 99.98 Neurotransmitter 2 99.64 Oxycodone 8 99.44 narcan 1 99.26 antagonist 12 99.08 Enkephalin 4 99.00 Opioid 1 98.86 antinociception 8 98.24 monoamine 34 94.48

Disease Link Frequency Relevance Heat Disease 301 99.50 Parkinson's Disease 108 99.26 Parkinsonian Disorders 8 97.92 Hypokinesia 8 97.20 Targeted Disruption 71 95.84 Muscle Rigidity 10 95.56 Tremor 4 94.80 Loss Of Sense Of Smell 3 91.40 Toxicity 29 82.64 Depression 5 73.84

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Moreover, starting after three MPTPp injections, we observed a gradual decline of TH-positive cells in the SNc, and a gradual raise of enkephalin mRNA in the CPu.

Negative_regulation (decline) of SNc in CPu associated with enkephalin

1) Confidence 0.20 Published 2009 Journal Neurotox Res Section Abstract Doc Link 19526289 Disease Relevance 0.56 Pain Relevance 0.40

Opioid-antagonist naloxone, completely blocked antinociceptive effect of DAMGO, SNC80, U50,488H or oxycodone and potentiation of antinociception by BMS182874.

Negative_regulation (effect) of SNC80 associated with antinociception, oxycodone, antagonist, narcan, antinociceptive and opioid

2) Confidence 0.10 Published 2010 Journal Eur. J. Pharmacol. Section Abstract Doc Link 20303944 Disease Relevance 0 Pain Relevance 2.28

This reduction in TH-Ser(P)-19 in WT-Syn- and S129A-Syn-transduced SNc suggested that TH activity might also be reduced in a-Syn lentivirally transduced mice.

Negative_regulation (reduction) of SNc

3) Confidence 0.06 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878529 Disease Relevance 0 Pain Relevance 0.12

Silencing of the Pink1 gene expression did not induce Parkinson's disease phenotypes, including a loss of the dopaminergic neurons in the SNc and the neurotransmitter dopamine in the striatum.

Negative_regulation (loss) of SNc in striatum associated with dopamine, neurotransmitter and disease

4) Confidence 0.04 Published 2007 Journal International Journal of Biological Sciences Section Body Doc Link PMC1820878 Disease Relevance 0.51 Pain Relevance 0.10

Neuropathological examination of MPTP-treated mice revealed a progressive decrease in the number of TH-positive neurons in the SNc as early as 3 days after the MPTP treatment as compared to the saline-treated mouse brains.

Negative_regulation (decrease) of SNc in neurons associated with parkinson's disease

5) Confidence 0.03 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2675062 Disease Relevance 0.92 Pain Relevance 0

Indeed, systemic exposure to paraquat provoked a dose-dependent loss of DA neurons in the SNc [8, 38], coupled with a reduction in the density of striatal DA fibres expressing tyrosine hydroxylase, the rate-limiting enzyme in DA synthesis [39].

Negative_regulation (loss) of SNc in DA neurons associated with dopamine

6) Confidence 0.02 Published 2011 Journal Parkinson's Disease Section Body Doc Link PMC3018622 Disease Relevance 1.00 Pain Relevance 0.29

60% SNc DA neuron loss, comprises a constellation of well-defined motor symptoms, including bradykinesia, hypokinesia (or akinesia), cogwheel rigidity, resting tremor, and postural instability [1].

Negative_regulation (loss) of SNc in DA neuron associated with tremor, dopamine, hypokinesia and muscle rigidity

7) Confidence 0.02 Published 2011 Journal Parkinson's Disease Section Body Doc Link PMC3018622 Disease Relevance 1.48 Pain Relevance 0.37

Critically, the loss of TH+ cells in the SNc was mirrored by an equivalent reduction in NeuN+ cells in the lesioned SNc in vehicle-treated animals (67.43 ± 1.15% [95% CI: 64.74%–69.95%]).

Negative_regulation (reduction) of SNc

8) Confidence 0.01 Published 2010 Journal Parkinson's Disease Section Body Doc Link PMC2951138 Disease Relevance 0.06 Pain Relevance 0.03

Critically, the loss of TH+ cells in the SNc was mirrored by an equivalent reduction in NeuN+ cells in the lesioned SNc in vehicle-treated animals (67.43 ± 1.15% [95% CI: 64.74%–69.95%]).

Negative_regulation (loss) of SNc

9) Confidence 0.01 Published 2010 Journal Parkinson's Disease Section Body Doc Link PMC2951138 Disease Relevance 0.06 Pain Relevance 0

In the current study we also observed that the neuroprotective effects of 2R,4R-APDC were associated with a qualitative decrease in microglial markers in the SNc.

Negative_regulation (decrease) of SNc

10) Confidence 0.01 Published 2010 Journal Parkinson's Disease Section Body Doc Link PMC2951138 Disease Relevance 0.25 Pain Relevance 0.14

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