Cyclic Nucleotide Phosphodiesterases (PDEs)—from Basic Insights to Structure, Physiologic Roles and Drug Development

Dear Colleagues,

The second messengers cAMP and cGMP transduce the action of a plethora of extracellular signals, ranging from hormones and neurotransmitters to proton gradients and light, into the most diverse cellular and physiologic responses, including vision, memory, cognition, or growth.  The intracellular concentration of these cyclic nucleotides is determined by the equilibrium between the rate of their production by adenylyl or guanylyl cyclases, and the rate of their hydrolysis and inactivation by phosphodiesterases (PDEs). The mammalian PDEs comprise a superfamily of enzymes that are encoded by 21 genes and are likely expressed as up to 100 distinct protein variants in the body. It is now appreciated that PDEs do not simply serve to terminate cyclic nucleotide signals.  PDEs finetune cyclic nucleotide gradients across the cell and are vital for the generation of subcellular compartments or microdomains of cyclic nucleotide signalling. These, in turn, are essential to accurately convey the information encoded in the multitude of extracellular signals, that act on the same cells to produce a variety of distinct responses, and yet use the same cyclic nucleotide as intracellular second messenger. Given the broad range of physiologic and pathophysiologic paradigms affected by cyclic nucleotide signalling, PDEs have also been recognized as promising drug targets, thus further heightening interest in these enzymes.

This Special Issue welcomes original research, short communications, and review manuscripts broadly related to the structure or compartmentalization of PDEs, their cellular, physiologic, and pathophysiologic roles, and the development of PDE inhibitors as therapeutics.

Dr. Wito Richter
Guest Editor

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• cyclic nucleotide phosphodiesterases
• PDEs
• cAMP
• cGMP
• compartmentalization
• structure
• physiologic and pathologic states
• inhibitor/drug development