INT134786

Context Info Confidence 0.68 First Reported 2005 Last Reported 2011 Negated 1 Speculated 0 Reported most in Body Documents 17 Total Number 17 Disease Relevance 7.61 Pain Relevance 3.29

peptidase activity (Adam10) nucleocytoplasmic transport (Adam10) Golgi apparatus (Adam10) nucleus (Adam10) cytoplasm (Adam10)

Anatomy Link Frequency Notch 1 neuronal 1 brains 1 astrocytes 1 Adam10 (Mus musculus)

Pain Link Frequency Relevance Heat metalloproteinase 126 100.00 substance P 15 99.40 Inflammation 182 99.24 long-term potentiation 12 98.36 Inflammatory mediators 14 89.56 qutenza 15 84.44 cINOD 148 81.68 COX-2 inhibitor 3 69.84 cytokine 41 62.64 glial activation 7 54.76

Disease Link Frequency Relevance Heat Targeted Disruption 301 99.64 INFLAMMATION 221 99.24 Cognitive Disorder 160 98.92 Apoptosis 19 98.56 Amyloid Plaque 103 98.04 Cancer 38 94.32 Disease 615 92.88 Necrosis 16 92.00 Infection 41 91.60 Toxicity 19 76.72

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Interestingly, low levels of cholesterol leads to high expression of Adam10, coding for a protease also known as Kuzbanian, which is essential for Notch activation [55].

Gene_expression (expression) of Adam10 in Notch

1) Confidence 0.68 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2699037 Disease Relevance 0 Pain Relevance 0

Moreover, when Adam10 is not expressed Dll1 is overexpressed [56].

Neg (not) Gene_expression (expressed) of Adam10

2) Confidence 0.68 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2699037 Disease Relevance 0 Pain Relevance 0

In light of the latter observation, it is perhaps of little surprise that it has more recently been shown that ADAM10 and not ADAM17 or 9 is the physiologically relevant basal ?

Gene_expression (relevant) of ADAM10

3) Confidence 0.51 Published 2011 Journal Biochemistry Research International Section Body Doc Link PMC2989646 Disease Relevance 0.43 Pain Relevance 0.09

Like other ADAM family members, ADAM10 has a modular ectodomain structure and is synthesized as an inactive zymogen being activated only after enzymatic removal of its prodomain [35].

Gene_expression (synthesized) of ADAM10

4) Confidence 0.46 Published 2011 Journal Biochemistry Research International Section Body Doc Link PMC2989646 Disease Relevance 0.07 Pain Relevance 0.03

A moderate neuronal over-expression of ADAM10 in mice transgenic for human APP([V717I]) showed increased secretion of the neurotrophic soluble ?

Gene_expression (expression) of ADAM10 in neuronal associated with targeted disruption

5) Confidence 0.45 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2442055 Disease Relevance 0.90 Pain Relevance 0.65

production than when either enzyme was transfected into cells expressing only endogenous ADAM10 [35] suggesting that it was the removal specifically of the ADAM10 prodomain and subsequent activation of the enzyme that correlated with the level of ?

Gene_expression (expressing) of ADAM10

6) Confidence 0.40 Published 2011 Journal Biochemistry Research International Section Body Doc Link PMC2989646 Disease Relevance 0.20 Pain Relevance 0.09

-secretase is involved in inflammation is supported by the observation that ADAM-10 is expressed constitutively by astrocytes in the normal and inflamed human CNS [64].

Gene_expression (expressed) of ADAM-10 in astrocytes associated with inflammation

7) Confidence 0.40 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2442055 Disease Relevance 0.46 Pain Relevance 0.23

Specifically ADAM-10 produces the same growth-inhibitory products from Substance P (i.e., SP (1-7)) that Neprilysin does, so that loss of ADAM-10 expression actually results in loss of production of growth inhibitory peptides from Substance P.

Gene_expression (expression) of ADAM-10 associated with substance p

8) Confidence 0.39 Published 2006 Journal Breast Cancer Res. Treat. Section Abstract Doc Link 16583263 Disease Relevance 0.49 Pain Relevance 0.36

Specifically ADAM-10 produces the same growth-inhibitory products from Substance P (i.e., SP (1-7)) that Neprilysin does, so that loss of ADAM-10 expression actually results in loss of production of growth inhibitory peptides from Substance P.

Gene_expression (produces) of ADAM-10 associated with substance p

9) Confidence 0.39 Published 2006 Journal Breast Cancer Res. Treat. Section Abstract Doc Link 16583263 Disease Relevance 0.55 Pain Relevance 0.41

Expression of mutant catalytically inactive ADAM10 led to an enhancement of the number and size of amyloid plaques in the brains of double-transgenic mice.

Gene_expression (Expression) of ADAM10 in brains associated with targeted disruption and amyloid plaque

10) Confidence 0.39 Published 2008 Journal J Neuroinflammation Section Body Doc Link PMC2442055 Disease Relevance 0.94 Pain Relevance 0.38

(amphiregulin, Adam10) [61] were differentially expressed in any group of mice.

Gene_expression (expressed) of Adam10

11) Confidence 0.37 Published 2009 Journal Mol Cancer Section Body Doc Link PMC2667483 Disease Relevance 0.52 Pain Relevance 0.07

Overexpression of ADAM10 increases ?

Gene_expression (Overexpression) of ADAM10

12) Confidence 0.36 Published 2011 Journal Mol Brain Section Body Doc Link PMC3022812 Disease Relevance 0.25 Pain Relevance 0.05

At first glance, loss of ADAM-10 expression would be expected to result in decreased invasive capability, due to loss of matrix metalloprotease activity.

Gene_expression (expression) of ADAM-10

13) Confidence 0.30 Published 2006 Journal Breast Cancer Res. Treat. Section Abstract Doc Link 16583263 Disease Relevance 0.73 Pain Relevance 0.41

In contrast, the expression of an inactive mutant of ADAM10 worsened the pathology [243].

Gene_expression (expression) of ADAM10

14) Confidence 0.29 Published 2007 Journal Acta Neuropathol Section Body Doc Link PMC2100431 Disease Relevance 0.65 Pain Relevance 0.07

Transgenic mice that have an overexpression of disintegrin and metalloprotease-10 (ADAM-10), which activates ?

Gene_expression (overexpression) of metalloprotease-10 associated with targeted disruption

15) Confidence 0.29 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2536544 Disease Relevance 0.71 Pain Relevance 0.19

Transgenic mice that have an overexpression of disintegrin and metalloprotease-10 (ADAM-10), which activates ?

Gene_expression (overexpression) of ADAM-10 associated with targeted disruption

16) Confidence 0.29 Published 2008 Journal Neuropsychiatric Disease and Treatment Section Body Doc Link PMC2536544 Disease Relevance 0.71 Pain Relevance 0.19

Ultimately, the integral cell-surface metalloproteinases ADAM-10 and ADAM-17/TACE were found to underlie ?

Gene_expression (found) of metalloproteinases ADAM-10 associated with metalloproteinase

17) Confidence 0.09 Published 2005 Journal PLoS Medicine Section Body Doc Link PMC543463 Disease Relevance 0 Pain Relevance 0.05

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