Protein folding disorders comprise a rapidly growing group of diseases that involve virtually every organ system and affect individuals of all ages. Their principal pathology is the inability of a protein to acquire or maintain its physiological three-dimensional structure. In cells, this generally results in one of three outcomes: accumulation of misfolded protein aggregates, cell death, or recognition by cellular quality control machinery and rapid degradation. Large-scale screening efforts to identify and design small molecules that either repair the folding defect or enable the protein to escape degradation have been encouraging. However, most compounds identified to date restore only a small fraction of molecules to the normal folding pathway, and hence are relatively poor therapeutic candidates. Results published by Wang et al. in this issue of the Biochemical Journal show that, for mutant forms of two ABC (ATP-Binding-Cassette) transporters, P-glycoprotein and CFTR (cystic fibrosis transmembrane conductance regulator), modest correction of trafficking by single agents can be additive when multiple compounds are used in combination. These findings raise the intriguing possibility that corrector molecules acting at different steps along the folding pathway might provide a multidrug approach to human protein folding disorders.
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September 2007
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Commentary|
August 13 2007
Pharmacological chaperoning: two ‘hits’ are better than one
William R. Skach
William R. Skach
1
1Department of Biochemistry and Molecular Biology, 3181 SW Sam Jackson Park Road, MC-L224, Oregon Health & Sciences University, Portland, OR 97239, U.S.A.
1email skachw@ohsu.edu
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Publisher: Portland Press Ltd
Received:
July 09 2007
Revision Received:
July 16 2007
Accepted:
July 17 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem J (2007) 406 (2): e1.
Article history
Received:
July 09 2007
Revision Received:
July 16 2007
Accepted:
July 17 2007
Connected Content
This is a correction to:
Additive effect of multiple pharmacological chaperones on maturation of CFTR processing mutants
Citation
William R. Skach; Pharmacological chaperoning: two ‘hits’ are better than one. Biochem J 1 September 2007; 406 (2): e1. doi: https://doi.org/10.1042/BJ20070896
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