INT69221

Context Info Confidence 0.56 First Reported 1997 Last Reported 2010 Negated 2 Speculated 0 Reported most in Body Documents 14 Total Number 15 Disease Relevance 10.57 Pain Relevance 1.83

mitochondrion (Sod1) aging (Sod1) peroxisome (Sod1) intracellular (Sod1) protein complex (Sod1) cytoplasm (Sod1)

Anatomy Link Frequency spinal 2 spinal cord 1 alveolar macrophages 1 brain 1 NMJs 1 Sod1 (Mus musculus)

Pain Link Frequency Relevance Heat Spinal cord 69 99.64 cytokine 80 97.24 Glutamate 104 93.96 Inflammation 167 91.96 COX2 1 90.72 ischemia 9 88.40 nMDA receptor 4 83.60 Pain 8 78.40 medulla 8 74.24 antagonist 23 72.16

Disease Link Frequency Relevance Heat Targeted Disruption 193 99.86 Syndrome 1 99.60 Cancer 269 99.54 Nicotine Addiction 49 99.20 Motor Neuron Diseases 649 97.64 Lifespan 25 97.44 Disease Progression 38 95.98 Respiratory Failure 3 95.64 Disease 206 95.30 Muscle Weakness 2 94.68

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

However, dramatic reduction of copper in SOD1 by knocking out the copper chaperon for SOD1 (CCS), or by mutating the copper chelating residues, did not affect ALS progression in vivo [36,48].

Negative_regulation (reduction) of SOD1 associated with motor neuron diseases

1) Confidence 0.56 Published 2003 Journal BMC Neurosci Section Body Doc Link PMC169170 Disease Relevance 0.49 Pain Relevance 0

However, the FALS syndrome results not from a loss of SOD1 function but rather a toxic gain of function [2].

Neg (not) Negative_regulation (loss) of SOD1 associated with syndrome

2) Confidence 0.55 Published 2006 Journal BMC Neurosci Section Body Doc Link PMC1488864 Disease Relevance 1.52 Pain Relevance 0.03

The increased ROS levels experienced by cells in wounded tissue may be exacerbated by the depletion of antioxidant enzymes including Cu/Zn superoxide dismutase (SOD1) and glutathione peroxidase [19].

Negative_regulation (depletion) of SOD1

3) Confidence 0.43 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2850366 Disease Relevance 0.73 Pain Relevance 0.15

The elevated expression of MnSOD, Cu/ZnSOD, reactive oxygen species (ROS), and reduction in glutathione, indicate altered redox balance upon LPS, A?

Negative_regulation (species) of Cu/ZnSOD

4) Confidence 0.41 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1262754 Disease Relevance 0.37 Pain Relevance 0.26

Interestingly, mRNA levels of the suppressor of cytokine signaling 1 and 3 genes were increased by Pio, whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected.

Neg (unaffected) Negative_regulation (unaffected) of SOD1 associated with targeted disruption and cytokine

5) Confidence 0.37 Published 2005 Journal J. Neurosci. Section Abstract Doc Link 16120782 Disease Relevance 0.67 Pain Relevance 0.27

Thus the inhibitory effect of Zn2+ in the spinal cord appears to be magnified by glutamatergic and glycinergic activity while that in the brain is not.

Negative_regulation (effect) of Zn2 in brain associated with spinal cord

6) Confidence 0.37 Published 1997 Journal Eur. J. Pharmacol. Section Abstract Doc Link 9137921 Disease Relevance 0 Pain Relevance 0.57

Ammonium tetrathiomolybdate (TTM) is a copper-chelating drug that is capable of removing a copper ion from copper-thiolate clusters, such as SOD1.104 A recent preclinical study on SOD1 transgenic mice found that treatment with TTM significantly delayed disease onset, slowed disease progression, and prolonged survival by approximately 20%, 42%, and 25%, respectively.104 TTM was also effective in depressing the spinal copper ion level and inhibiting the lipid peroxidation, with a significant suppression of SOD1 enzymatic activity in SOD1.104 There are still no data on humans.

Negative_regulation (suppression) of SOD1 in spinal associated with targeted disruption, disease and disease progression

7) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785861 Disease Relevance 0.89 Pain Relevance 0

Ammonium tetrathiomolybdate (TTM) is a copper-chelating drug that is capable of removing a copper ion from copper-thiolate clusters, such as SOD1.104 A recent preclinical study on SOD1 transgenic mice found that treatment with TTM significantly delayed disease onset, slowed disease progression, and prolonged survival by approximately 20%, 42%, and 25%, respectively.104 TTM was also effective in depressing the spinal copper ion level and inhibiting the lipid peroxidation, with a significant suppression of SOD1 enzymatic activity in SOD1.104 There are still no data on humans.

Negative_regulation (suppression) of SOD1 in spinal associated with targeted disruption, disease and disease progression

8) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785861 Disease Relevance 0.88 Pain Relevance 0

Edaravone (MCI-186) is an agent widely used for cerebral ischemia in Japan that acts as a free-radical scavenger.94 In a randomized blind trial, intraperitoneally administration of multiple doses of edaravone in an ALS mice model significantly slowed the motor decline and motor neuron degeneration of the transgenic mice, even when administered after the onset of the disease.94 Furthermore, high-dose eda-varone treatment was associated with a significant decrease in the area of mutant SOD1 deposition in the spinal cord.94 The favorable effects of the drug might be attributable to its primary antioxidant properties or alternatively to the reduction of mutant SOD1 accumulation.94

Negative_regulation (reduction) of SOD1 in spinal cord associated with targeted disruption, cv general 4 under development, ischemia, disease, nerve degeneration, motor neuron diseases and spinal cord

9) Confidence 0.32 Published 2009 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2785861 Disease Relevance 0.97 Pain Relevance 0.15

Recently, Juarez et al, have shown that TM attenuates angiogenesis and tumor cell proliferation by inhibiting superoxide dismutase 1 (SOD1) [30].

Negative_regulation (inhibiting) of SOD1 associated with cancer

10) Confidence 0.28 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2922193 Disease Relevance 1.36 Pain Relevance 0.07

Recently, Juarez et al, have shown that TM attenuates angiogenesis and tumor cell proliferation by inhibiting superoxide dismutase 1 (SOD1) [30].

Negative_regulation (inhibiting) of superoxide dismutase 1 associated with cancer

11) Confidence 0.28 Published 2010 Journal Mol Cancer Section Body Doc Link PMC2922193 Disease Relevance 1.36 Pain Relevance 0.07

The activities of CuZnSOD, glutathione-S-transferase and glutathione peroxidase (GP) are all decreased in alveolar macrophages from elderly smokers (Gilks et al 1998).

Negative_regulation (decreased) of CuZnSOD in alveolar macrophages associated with nicotine addiction

12) Confidence 0.18 Published 2007 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2695202 Disease Relevance 0.57 Pain Relevance 0.03

Unexpectedly, the expression of the enzymes that directly scavenge ROS decreased, including superoxide dismutases 1 and 2, glutathione peroxidase 1, and catalase.

Negative_regulation (decreased) of superoxide dismutases 1

13) Confidence 0.18 Published 2007 Journal International Journal of Biological Sciences Section Abstract Doc Link PMC1925139 Disease Relevance 0.08 Pain Relevance 0

In strong support of this work are reports indicating that GH overexpression in vivo suppresses catalase and SOD1, increases tissue oxidative damage, and significantly shortens lifespan (Brown-Borg and Rakoczy 2000; Brown-Borg et al. 1999, 2001b, 2002; Hauck and Bartke 2001; Pendergrass et al. 1993; Wolf et al. 1993; Rollo et al. 1996).

Negative_regulation (suppresses) of SOD1 associated with lifespan

14) Confidence 0.16 Published 2006 Journal Age (Dordr) Section Body Doc Link PMC2464727 Disease Relevance 0.33 Pain Relevance 0

In control mice, almost all NMJs were innervated by motor neurons, an innervation that was markedly reduced in the Sod1G93A;Vglut2flox/+ mouse.

Negative_regulation (reduced) of Sod1G93A in NMJs

15) Confidence 0.05 Published 2010 Journal Upsala Journal of Medical Sciences Section Body Doc Link PMC2853350 Disease Relevance 0.36 Pain Relevance 0.23

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