title: Glucocerebrosidase inhibitors for the treatment of Gaucher disease.
abstract: Gaucher disease is a progressive lysosomal storage disorder caused by a deficiency in the activity of β-glucocerebrosidase and is characterized by the accumulation of the glycosphingolipid glucosylceramide in the lysosomes of macrophages that leads to dysfunction in multiple organ system. An emerging strategy for the treatment of Gaucher disease is pharmacological chaperone therapy, based on the use of β-glucocerebrosidase inhibitors that are capable of enhancing residual hydrolytic activity at subinhibitory concentrations. In this article, the most common lysosomal storage disorder, Gaucher disease, is introduced and the current therapeutic strategies based on the use of enzyme inhibitors to ameliorate this disease are discussed, with a focus on the efforts being made toward finding and optimizing novel molecules as pharmacological chaperones for Gaucher disease that offer the promise to remedy this malady.
authors.affiliation: Laboratory of Medicinal Chemistry, Department of Biomedicinal Chemistry, Institut de Química Avançada de Catalunya (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Trapero
authors.forename: Amadeu
authors.initials: A
authors.lastname: Llebaria
mesh_terms: D000818:Animals; D054812:Cyclitols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D005776:Gaucher Disease / Q000188:drug therapy* / Q000201:enzymology*; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D050111:Imino Sugars / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008958:Models, Molecular
chemical_list: D054812:Cyclitols; D004791:Enzyme Inhibitors; D050111:Imino Sugars; D005962:Glucosylceramidase