The chaperone activity and toxicity of ambroxol on Gaucher cells and normal mice

Brain Dev. 2013 Apr;35(4):317-22. doi: 10.1016/j.braindev.2012.05.008. Epub 2012 Jun 7.


Gaucher disease (GD), caused by a defect of acid β-glucosidase (β-Glu), is one of the most common sphingolipidoses. Recently, ambroxol, an FDA-approved drug used to treat airway mucus hypersecretion and hyaline membrane disease in newborns, was identified as a chemical chaperone for GD. In the present study, we investigated the chaperone activity and toxicity of ambroxol on both cultured GD patient cells and normal mice. We found that ambroxol treatment significantly increased N370S, F213I, N188S/G193W and R120W mutant β-Glu activities in GD fibroblasts with low cytotoxicity. Additionally, we measured the β-Glu activity in the tissues of normal mice which received water containing increasing concentrations of ambroxol ad libitum for one week. No serious adverse effect was observed during this experiment. Ambroxol significantly increased the β-Glu activity in the spleen, heart and cerebellum of the mice. This result showed its oral availability and wide distribution and chaperone activity in the tissues, including the brain, and its lack of acute toxicity. These characteristics of ambroxol would make it a potential therapeutic chaperone in the treatment of GD with neurological manifestations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ambroxol / pharmacology*
  • Animals
  • Body Weight / drug effects
  • Cells, Cultured
  • Colorimetry
  • Dose-Response Relationship, Drug
  • Drinking / drug effects
  • Expectorants / pharmacology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fluorescent Dyes / pharmacokinetics
  • Galactosides / pharmacokinetics
  • Gaucher Disease / pathology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / genetics
  • Humans
  • Hymecromone / analogs & derivatives
  • Hymecromone / pharmacokinetics
  • Mice
  • Mice, Inbred C57BL
  • Molecular Chaperones / blood
  • Molecular Chaperones / metabolism*
  • Molecular Chaperones / urine
  • Mutation / genetics
  • Skin / pathology
  • Time Factors
  • beta-Glucosidase / genetics


  • Expectorants
  • Fluorescent Dyes
  • Galactosides
  • Molecular Chaperones
  • Ambroxol
  • Hymecromone
  • 4-methylumbelliferyl-galactopyranoside
  • beta-Glucosidase