Chemical and pharmacological chaperones as new therapeutic agents

TW Loo, DM Clarke - Expert reviews in molecular medicine, 2007 - cambridge.org
TW Loo, DM Clarke
Expert reviews in molecular medicine, 2007cambridge.org
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 …
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.
Cambridge University Press