Chasing a Breath of Fresh Air in Cystic Fibrosis (CF): Therapeutic Potential of Selective HDAC6 Inhibitors to Tackle Multiple Pathways in CF Pathophysiology

Compelling new support has been provided for histone deacetylase isoform 6 (HDAC6) as a common thread in the generation of the dysregulated proinflammatory and fibrotic phenotype in cystic fibrosis (CF). HDAC6 also plays a crucial role in bacterial clearance or killing as a direct consequence of its...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2022-02, Vol.65 (4), p.3080-3097
Main Authors: Barone, Simona, Cassese, Emilia, Alfano, Antonella Ilenia, Brindisi, Margherita, Summa, Vincenzo
Format: Article
Language:English
Subjects:
Animals
Cystic Fibrosis - drug therapy
Cystic Fibrosis - physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator
Histone Deacetylase 6 - antagonists & inhibitors
Humans
Signal Transduction - drug effects
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Summary:Compelling new support has been provided for histone deacetylase isoform 6 (HDAC6) as a common thread in the generation of the dysregulated proinflammatory and fibrotic phenotype in cystic fibrosis (CF). HDAC6 also plays a crucial role in bacterial clearance or killing as a direct consequence of its effects on CF immune responses. Inhibiting HDAC6 functions thus eventually represents an innovative and effective strategy to tackle multiple aspects of CF-associated lung disease. In this Perspective, we not only showcase the latest evidence linking HDAC(6) activity and expression with CF phenotype but also track the new dawn of HDAC(6) modulators in CF and explore potentialities and future perspectives in the field.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.1c02067