INT234869

Context Info Confidence 0.12 First Reported 2008 Last Reported 2008 Negated 0 Speculated 1 Reported most in Body Documents 1 Total Number 6 Disease Relevance 5.34 Pain Relevance 0.11

cell adhesion (Dsg2) plasma membrane (Dsg2)

Anatomy Link Frequency other parts 2 Dsg2 (Mus musculus)

Pain Link Frequency Relevance Heat metalloproteinase 36 75.40 Kinase C 78 72.08 Inflammatory mediators 6 37.32 agonist 30 5.00 corticosteroid 12 5.00 addiction 12 5.00 Pain 6 5.00 imagery 6 5.00 antagonist 6 5.00

Disease Link Frequency Relevance Heat Bullous Skin Disease 1824 99.74 Adhesions 306 98.60 Acantholysis 390 95.12 Streptococcus Infection 12 91.48 Stress 24 79.20 Apoptosis 114 51.88 Blister 72 44.84 Autoimmune Disease 24 42.60 INFLAMMATION 6 36.92 Disease 108 21.04

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The major goal for the future is to elucidate the primary signalling pathways responsible for the diverse effects of pemphigus IgG such as inhibition of desmoglein binding, depletion of desmosomal components, loss of desmosomes, reorganization of the cytoskeleton and finally the induction of acantholysis.

Negative_regulation (inhibition) of desmoglein Binding (binding) of associated with acantholysis and bullous skin disease

1) Confidence 0.12 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.37 Pain Relevance 0.04

Later on, with the identification of desmosomal cadherins as the target antigens of pemphigus autoantibodies and with more sophisticated cell biologic tools at hand, the ideas of direct antibody-mediated inhibition and of indirect signalling-mediated reduction of desmoglein binding were developed (Fig. 8).

Negative_regulation (reduction) of desmoglein Binding (binding) of associated with bullous skin disease

2) Confidence 0.12 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.01 Pain Relevance 0

An antibody directed against the putative transadhesive interface may directly induce steric hindrance, whereas antibodies directed against other parts of the desmoglein ectodomain could indirectly inhibit desmoglein binding by allosteric mechanisms.

Negative_regulation (inhibit) of desmoglein Binding (binding) of in other parts

3) Confidence 0.12 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.26 Pain Relevance 0

Since it was discovered that autoantibodies in pemphigus are directed to desmosomal adhesion molecules, it was believed that these autoantibodies might directly interfere with desmoglein binding (Fig. 8) (Amagai et al. 1991; Jones et al. 1986a; Koulu et al. 1984), a mechanism also refered to as “steric hindrance”(Sharma et al. 2007).

Spec (might) Negative_regulation (interfere) of desmoglein Spec (might) Binding (binding) of associated with bullous skin disease and adhesions

4) Confidence 0.09 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.15 Pain Relevance 0.03

Therefore, “direct inhibition”, instead of “steric hindrance” of desmoglein binding should be used until discrimination between steric and allosteric effects is possible.

Negative_regulation (hindrance) of desmoglein Binding (binding) of

5) Confidence 0.09 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 0.31 Pain Relevance 0

Direct inhibition of desmoglein binding

Negative_regulation (inhibition) of desmoglein Binding (binding) of

6) Confidence 0.09 Published 2008 Journal Histochem Cell Biol Section Body Doc Link PMC2413110 Disease Relevance 1.25 Pain Relevance 0.04

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