Phosphodiesterases (PDEs): Therapeutic Targets in Human Health and Disease

Dear Colleagues,

In 1957, when Earl Sutherland and Ted Rall discovered cAMP as the first “second messenger” mediating the effects of hormones on liver and skeletal muscle, the field of signal transduction, the way in which cells communicate with each other and respond to external signals, was born. It is apparent now that many diseases result from something going wrong in these signal transduction processes, and correcting the spatial and temporal changes in cAMP levels in subcellular compartments back to normal can therapeutically treat these resultant diseases. An enzymatic activity, cAMP phosphodiesterase (PDE), capable of converting cAMP to 5’-AMP, which terminates the messenger function of cAMP, was reported at the time of its discovery. We now know that PDEs represent a superfamily of enzymes encoded by 21 different genes grouped into 11 gene families.  More than 100 different forms of PDE have now been identified, some of which are selectively located in different cell types and in different subcellular compartments. With this degree of complexity, by inhibiting or altering the expression of specific forms of PDE, we can change fundamental physiological processes in one cell type, without affecting others, which is the basis and goal of targeted therapies. To this end, efforts have been focused on which PDEs mediate which cell processes and on developing selective inhibitors of these PDEs to correct a wide variety of disease states. Drugs that target PDEs have now been approved for COPD, psoriasis, atopic dermatitis, erectile dysfunction, pulmonary hypertension, and heart failure. And this is only the tip of the iceberg, as they also show therapeutic benefits for a wide range of cancers, CNS disorders, autoimmune disorders, and metabolic disorders.

The aim of this Special Issue is to highlight recent advances in targeting PDEs for therapeutic benefit, and we would be delighted to have you join us in this by submitting your recent work.

Dr. Paul M. Epstein
Dr. Stefan Brocke
Dr. Michy P. Kelly
Dr. Leila Gobejishvili
Guest Editors

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• cyclic nucleotide phosphodiesterase
• PDE
• cAMP
• cGMP
• signal transduction