Chemical and pharmacological chaperones as new therapeutic agents
- 28 June 2007
- journal article
- review article
- Published by Cambridge University Press (CUP) in Expert Reviews in Molecular Medicine
- Vol. 9 (16) , 1-18
Abstract
Proteins that are exported from the cell, or targeted to the cell surface or other organelles, are synthesised and assembled in the endoplasmic reticulum and then delivered to their destinations. Point mutations – the most common cause of human genetic diseases – can inhibit folding and assembly of the protein in the endoplasmic reticulum. The unstable or partially folded mutant protein does not undergo trafficking and is usually rapidly degraded. A potential therapy for protein misfolding is to correct defective protein folding and trafficking using pharmacological chaperones. Pharmacological chaperones are substrates or modulators that appear to function by directly binding to the partially folded biosynthetic intermediate to stabilise the protein and allow it to complete the folding process to yield a functional protein. Initial clinical studies with pharmacological chaperones have successfully reduced clinical symptoms of disease. Therefore, pharmacological chaperones show great promise as a new class of therapeutic agents that can be specifically tailored for a particular genetic disease.Keywords
This publication has 115 references indexed in Scilit:
- Isofagomine- and 2,5-Anhydro-2,5-imino-d-glucitol-Based Glucocerebrosidase Pharmacological Chaperones for Gaucher Disease InterventionJournal of Medicinal Chemistry, 2006
- G-Protein-Coupled Receptor Trafficking: Understanding the Chemical Basis of Health and DiseaseACS Chemical Biology, 2006
- A Mutation Linked with Autism Reveals a Common Mechanism of Endoplasmic Reticulum Retention for the α,β-Hydrolase Fold Protein FamilyJournal of Biological Chemistry, 2006
- Rescue of ΔF508 and Other Misprocessed CFTR Mutants by a Novel Quinazoline CompoundMolecular Pharmaceutics, 2005
- Human Gene Mutation Database (HGMD®): 2003 updateHuman Mutation, 2003
- Pharmacological Rescue of Mutant p53 Conformation and FunctionScience, 1999
- Nonylphenol Ethoxylates, but Not Nonylphenol, Are Substrates of the Human Multidrug Resistance P-glycoproteinBiochemical and Biophysical Research Communications, 1998
- Glycerol Reverses the Misfolding Phenotype of the Most Common Cystic Fibrosis MutationJournal of Biological Chemistry, 1996
- Galactose Stabilizes Various Missense Mutants of α-Galactosidase in Fabry DiseaseBiochemical and Biophysical Research Communications, 1995
- Characterization of a Mutant α-Galactosidase Gene Product for the Late-Onset Cardiac Form of Fabry DiseaseBiochemical and Biophysical Research Communications, 1993