Chemical and pharmacological chaperones as new therapeutic agents

Tip W. Loo; David M. Clarke

doi:10.1017/S1462399407000361

Chemical and pharmacological chaperones as new therapeutic agents

Published online by Cambridge University Press: 28 June 2007

Tip W. Loo and

David M. Clarke

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Tip W. Loo: Affiliation:
Department of Medicine and Department of Biochemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
David M. Clarke*: Affiliation:
Department of Medicine and Department of Biochemistry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
*: *Corresponding author: David M. Clarke, Department of Medicine, University of Toronto, Rm 7342, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada. Tel/Fax: +1 416 978 1105; E-mail: david.clarke@utoronto.ca

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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.

Type: Review Article
Information: Expert Reviews in Molecular Medicine , Volume 9 , Issue 16 , June 2007 , pp. 1 - 18

DOI: https://doi.org/10.1017/S1462399407000361 [Opens in a new window]
Copyright: Copyright © Cambridge University Press 2007

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Chemical and pharmacological chaperones as new therapeutic agents

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