[Pharmacological chaperones: a potential therapeutic treatment for conformational diseases].
Many genetic and neurodegenerative diseases in humans result from protein misfolding and/or aggregation. These diseases are named conformational diseases. As a result, the misfolded non functional proteins are rejected and misrouted by the cellular quality control system, and cannot play their endogenous physiological roles. Specific compounds (ligands, substrates or inhibitors) known as pharmacological chaperones are able to bind and stabilize these misfolded proteins. Their interaction allows the target proteins to escape the quality control system and to be functionally rescued. These pharmacochaperones may possess different intrinsic activity: they can be antagonists (inhibitors), agonists (activators) or allosteric modulators of the target receptors, ionic channels or enzymes. Pharmacological chaperones have obviously a therapeutic potential to treat rare diseases like cystic fibrosis, retinitis pigmentosa, nephrogenic diabetes insipidus, Fabry disease, Gaucher disease, but also for cancers and more frequent and highly invalidant neurodegenerative disorders such as Alzheimer's disease or Parkinson's disease.
Mendre
Christiane
C
Universités Montpellier 1 et 2, 141, 34094 Montpellier Cedex 05, France. christiane.mendre@igf.cnrs.fr
Mouillac
Bernard
B
D041321:Chromosomes, Human, X; D003550:Cystic Fibrosis / Q000235:genetics; D018500:Diabetes Insipidus, Nephrogenic / Q000235:genetics; D000795:Fabry Disease / Q000235:genetics; D005776:Gaucher Disease / Q000235:genetics; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D057165:Proteostasis Deficiencies / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics
D018832:Molecular Chaperones; D007987:Gonadotropin-Releasing Hormone