Molecular mechanisms of cystic fibrosis - how mutations lead to misfunction and guide therapy.
CFTR
Cystic Fibrosis
Molecular basis of disease
Mutations
Theratypes
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
29 07 2022
29 07 2022
Historique:
received:
03
05
2022
revised:
03
06
2022
accepted:
13
06
2022
pubmed:
17
6
2022
medline:
6
7
2022
entrez:
16
6
2022
Statut:
ppublish
Résumé
Cystic fibrosis, the most common autosomal recessive disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes a cAMP-activated chloride and bicarbonate channel that regulates ion and water transport in secretory epithelia. Although all mutations lead to the lack or reduction in channel function, the mechanisms through which this occurs are diverse - ranging from lack of full-length mRNA, reduced mRNA levels, impaired folding and trafficking, targeting to degradation, decreased gating or conductance, and reduced protein levels to decreased half-life at the plasma membrane. Here, we review the different molecular mechanisms that cause cystic fibrosis and detail how these differences identify theratypes that can inform the use of directed therapies aiming at correcting the basic defect. In summary, we travel through CFTR life cycle from the gene to function, identifying what can go wrong and what can be targeted in terms of the different types of therapeutic approaches.
Identifiants
pubmed: 35707985
pii: 231430
doi: 10.1042/BSR20212006
pmc: PMC9251585
pii:
doi:
Substances chimiques
RNA, Messenger
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 The Author(s).
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