title: Efficacy of magnesium chloride in the treatment of Hailey-Hailey disease: from serendipity to evidence of its effect on intracellular Ca(2+) homeostasis.
abstract: BACKGROUND
  Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited intraepidermal blistering genodermatosis. Mutations in the ATP2C1 gene encoding for the Golgi secretory pathway Ca(2+) /Mn(2+) -ATPasi protein 1 (SPCA1) affect the processing of desmosomal components and the epidermal suprabasal cell-cell adhesion by deregulating the keratinocyte cytosolic Ca(2+) concentration. We report the unexpected, dramatic, and persistent clinical improvement of the skin lesions of a patient affected with longstanding HHD with daily intake of a solution containing magnesium chloride hexahydrate (MgCl2 ).
  
  
  METHODS
  We investigated the effect of MgCl2 on the intracellular Ca(2+) homeostasis and on the activity of particular Ca(2+) -effectors in HeLa cells transfected with chimeric aequorins (cytAEQ, mtAEQ, erAEQ and GoAEQ) targeted to different subcellular compartments (cytosol, mitochondria, endoplasmic reticulum, and Golgi, respectively).
  
  
  RESULTS
  Experimental investigations on HeLa cells showed the effect of MgCl2 on the function of Ca(2+) -extrusor systems, resulting in increased cytosolic and mitochondrial Ca(2+) levels, without altering the mechanisms of intraluminal Ca(2+) -filling and Ca(2+) -release of stores.
  
  
  CONCLUSIONS
  Based on our clinical observation and experimental results, it can be hypothesized that MgCl2 could act as an inhibitor of the Ca(2+) -extruding activity in keratinocytes favoring intracellular Ca(2+) -disponibility and Ca(2+) -dependent mechanisms in desmosome assembly. This may represent the molecular basis of the good response of the HHD clinical features with MgCl2 solution in the patient described.
authors.affiliation: Department of Medical Sciences, Section of Dermatology, University of Ferrara, Ferrara, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Borghi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rimessi
authors.forename: Sara
authors.initials: S
authors.lastname: Minghetti
authors.forename: Monica
authors.initials: M
authors.lastname: Corazza
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Annarosa
authors.initials: A
authors.lastname: Virgili
mesh_terms: D000368:Aged; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D015603:Keratinocytes; D015636:Magnesium Chloride / Q000627:therapeutic use*; D016506:Pemphigus, Benign Familial / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015636:Magnesium Chloride; D002118:Calcium