Human epidermis shows a non-neuronal cholinergic system including keratinocyte (kc) acetylcholine (Ach)
axis which is composed by enzymes and two families of Ach receptors (muscarinic and nicotinic receptors). The activity
of these two receptors can regulate the interkeratinocytes and kcs-extracellular matrix adhesion modifying the regulation
of intercellular adhesion molecules like cadherins and integrins. Some authors demonstrate that acantholysis in pemphigus
depends not only on anti desmogleins antibodies (abs) (mostly IgG) but even on other abs directed against kc membrane
antigens (e.g. anti Ach receptors Abs). In the early phase of pemphigus pathogenesis, anti Ach receptors Abs block Ach
signaling essential for cell shape and intercellular adhesion and increase the phosphorylation of adhesion molecules.
Combined with the action of abs antidesmogleins, anti Ach receptors Abs cause the acantholytic phenomenon. In vitro
experiments show that high doses of Ach in acantholytic kcs can rapidly reverse this pathologic event. In vivo experiments
using neonatal mice model of Pemphigus have demonstrated that cholinergic agonists reduce these lesions. Therapy with
pyridostigmine bromide and Nicotinamide per os or pilocarpine used topically, drugs that present cholinomimetic effects,
has lead to encouraging results in patients affected by Pemphigus disease. Cholinergic agents could have a strategic role in
the therapy of pemphigus since they could be responsible for the early stage of acantholytic diseases.