Pharmacological chaperoning

two 'hits' are better than one.

William Skach

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalBiochemical Journal
Volume406
Issue number2
DOIs
StatePublished - Sep 1 2007

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Proteostasis Deficiencies
Protein folding
Pharmacology
Cystic Fibrosis Transmembrane Conductance Regulator
Molecules
ATP-Binding Cassette Transporters
P-Glycoprotein
Quality Control
Degradation
Proteins
Cell Death
Pathology
Cell death
Machinery
Quality control
Screening
Repair
Defects
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pharmacological chaperoning : two 'hits' are better than one. / Skach, William.

In: Biochemical Journal, Vol. 406, No. 2, 01.09.2007.

Research output: Contribution to journalArticle

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