Projects per year
Abstract
Cystic fibrosis (CF) mutations have complex effects on the cystic fibrosis transmembrane conductance regulator (CFTR) protein. They disrupt its processing to and stability at the plasma membrane and function as an ATP-gated Cl− channel. Here, we review therapeutic strategies to overcome defective CFTR processing and stability. Because CF mutations have multiple impacts on the assembly of CFTR protein, combination therapy with several pharmacological chaperones is likely to be required to rescue mutant CFTR expression at the plasma membrane. Alternatively, proteostasis regulators, proteins which regulate the synthesis, intracellular transport and membrane stability of CFTR might be targeted to enhance the plasma membrane expression of mutant CFTR. Finally, we consider an innovative approach to bypass CFTR dysfunction in CF, the delivery of artificial anion transporters to CF epithelia to shuttle Cl− across the apical membrane. The identification of therapies or combinations of therapies, which rescue all CF mutations, is now a priority.
Original language | English |
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Pages (from-to) | S14-S21 |
Number of pages | 8 |
Journal | Journal of Cystic Fibrosis |
Volume | 17 |
Issue number | 2 |
Early online date | 12 Sept 2017 |
DOIs | |
Publication status | Published - 1 Mar 2018 |
Keywords
- CFTR CI-channel
- F508del-CFTR
- CFTR correctors
- Pharmacological chaperones
- Proteostasis regulators
- Artificial anion transporters (anionophores)
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Dive into the research topics of 'Therapeutic approaches to CFTR dysfunction: from discovery to drug development'. Together they form a unique fingerprint.Projects
- 2 Finished
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Synthetic Anionophores with Therapeutic Potential - a Coordinated Two-Centre Approach
Davis, A. P. (Principal Investigator)
10/09/12 → 9/03/16
Project: Research
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SYNTHETIC ANION CARRIERS FOR BIOMEDICAL APPLICATIONS
Davis, A. P. (Principal Investigator)
1/11/08 → 1/03/12
Project: Research