Dear Colleagues,

Second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are central players in numerous biological processes such as cell proliferation and differentiation. Intracellular levels of cAMP and cGMP are tightly regulated by phosphodiesterases (PDEs), which are responsible for their hydrolysis in a temporal and spatial manner. Mammalian PDEs are encoded by 21 genes that, following splicing processes, give rise to more than 100 different isoforms in human and rodents. The broad expression of PDEs in many cell types and their ability to regulate a plethora of cellular functions have led to the development of several PDEs inhibitors. Many PDEs inhibitors have already been approved for the treatment of erectile dysfunction, pulmonary arterial hypertension and chronic obstructive pulmonary disease, and many others are currently under clinical evaluation. The complexity of cyclic nucleotides regulation requires a deep understanding of molecular and cellular mechanisms involved in PDEs signaling pathways.

This Research Topic aims to highlight the current understanding and recent advances of PDE signaling pathways in health and disease and to provide evidence on basic and translational research for the potential use of PDE inhibitors for the treatment of human disorders.

We welcome high-quality Original Articles, Methods, Commentaries and Review Articles that fall under the following topics:
- Molecular mechanisms of PDEs signaling pathways
- Development and characterization of mouse models to study cyclic nucleotides-PDEs signaling pathways
- Development and characterization of PDE inhibitors for the treatment of human disorders.

Dr. Federica Campolo

Guest Editor