Apoptolysis: a novel mechanism of skin blistering in XXXX linking the apoptotic pathways to basal cell shrinkage and suprabasal acantholysis.

@entity137 @entity7242 @entity7271 @entity3470 @entity460 @entity204
Understanding the acantholytic pathways leading to blistering in @entity7271 ( @entity7271 ) is a key to development of novel treatments. A novel paradigm of keratinocyte damage in @entity7271 , termed apoptolysis, links the suprabasal acantholytic and cell @entity204 pathways to basal cell shrinkage rendering a 'tombstone' appearance to @entity7271 . In contrast to apoptolysis, the classic keratinocyte apoptosis mediating @entity137 causes @entity204 and subsequent sloughing of the entire epidermis. Apoptolysis includes five consecutive steps. (1) Binding of autoantibodies to @entity7271 antigens. (2) Activation of EGF receptor, @entity7242 , @entity3470 , p38 MAPK and other signalling elements downstream of ligated antigens, elevation of intracellular @entity460 and launching of the cell @entity204 cascades. (3) Basal cell shrinkage due to: (i) collapse and retraction of the tonofilaments cleaved by executioner caspases; and (ii) dissociation of interdesmosomal adhesion complexes caused by phosphorylation of adhesion molecules. (4) Massive cleavage of cellular proteins by activated cell @entity204 enzymes leading to cell collapse, and tearing off desmosomes from the cell membrane stimulating secondary autoantibody production. (5) Rounding up and @entity204 of acantholytic cells. Thus, the structural damage (acantholysis) and @entity204 (apoptosis) of keratinocytes are mediated by the same cell @entity204 enzymes. Appreciation of the unifying concept of apoptolysis have several important implications: (i) linking together a number of seemingly unrelated events surrounding acantholysis; (ii) opening new avenues of investigation into the pathomechanism of pemphigus; and (iii) creating new approaches to the treatment of pemphigus based on blocking the signalling pathways and enzymatic processes that lead to blistering.
