Abstract
Sphingolipids are crucial molecules in the respiratory airways. As in most other tissues and organs, in the lung sphingolipids play an essential role as structural constituents as they regulate barrier function and fluidity of cell membranes. A lung-specific feature is the occurrence of sphingolipids as minor structural components in the surfactant. However, sphingolipids are also key signaling molecules involved in airway cell signaling and their dynamical formation and metabolism are important for normal lung physiology. Dysregulation of sphingolipid metabolism and signaling is involved in altering lung tissue and initiates inflammatory processes promoting the pathogenesis of pulmonal diseases including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma.
In the present review, the important role of specific sphingolipid species in pulmonal diseases will be discussed. Only such an understanding opens up the possibility of develo** new therapeutic strategies with the aim of correcting the imbalance in sphingolipid metabolism and signaling. Such delivery strategies have already been studied in animal models of these lung diseases, demonstrating that targeting the sphingolipid profile represents new therapeutic opportunities for lung disorders.
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Abbreviations
- CerS:
-
Ceramide synthase
- CERT:
-
Ceramide transporter
- CF:
-
Cystic fibrosis
- CFTR/Cftr:
-
Cystic fibrosis transmembrane conductance regulator
- COPD:
-
Chronic obstructive pulmonary disease
- IL:
-
Interleukin
- NF-κB:
-
Nuclear factor-κB
- ORMDL:
-
Orosomucoid-like
- S1P:
-
Sphingosine 1-phosphate
- S1PR:
-
S1P-Specific G-protein-coupled receptor
- SPHK:
-
Sphingosine kinase
- TNF-α:
-
Tumor necrosis factor α
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Kleuser, B., Schumacher, F., Gulbins, E. (2023). New Therapeutic Options in Pulmonal Diseases: Sphingolipids and Modulation of Sphingolipid Metabolism. In: Schäfer-Korting, M., Schubert, U.S. (eds) Drug Delivery and Targeting. Handbook of Experimental Pharmacology, vol 284. Springer, Cham. https://doi.org/10.1007/164_2023_700
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